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Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Classified gene: SEPHS1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5761 SEPHS1 Zornitza Stark gene: SEPHS1 was added
gene: SEPHS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092, SEPHS1-related
Review for gene: SEPHS1 was set to GREEN
Added comment: Nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo.
Sources: Literature
Mendeliome v1.1675 SEPHS1 Zornitza Stark Marked gene: SEPHS1 as ready
Mendeliome v1.1675 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Mendeliome v1.1675 SEPHS1 Zornitza Stark Classified gene: SEPHS1 as Green List (high evidence)
Mendeliome v1.1675 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Mendeliome v1.1674 SEPHS1 Zornitza Stark gene: SEPHS1 was added
gene: SEPHS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092, SEPHS1-related
Review for gene: SEPHS1 was set to GREEN
Added comment: Nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Marked gene: GLUL as ready
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from to Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015
Intellectual disability syndromic and non-syndromic v0.5759 GLUL Zornitza Stark Publications for gene: GLUL were set to
Intellectual disability syndromic and non-syndromic v0.5758 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5757 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: 16267323, 21353613, 33150193; Phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related, Glutamine deficiency, congenital MIM#610015, disorder of amino acid metabolism; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2544 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital MIM#610015 to Glutamine deficiency, congenital MIM#610015; Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related
Genetic Epilepsy v0.2543 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2542 GLUL Zornitza Stark edited their review of gene: GLUL: Added comment: Nine individuals with de novo variants in this gene and DEE. Seven out of nine were start-loss variants and two out of nine disrupted 5′ UTR splicing resulting in splice exclusion of the initiation codon.; Changed phenotypes: Glutamine deficiency, congenital MIM#610015, Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1673 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism to Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism
Mendeliome v1.1672 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1671 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v1.12 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Hereditary Neuropathy - complex v1.12 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.12 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Hereditary Neuropathy - complex v1.12 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Ataxia - adult onset v1.8 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Ataxia - adult onset v1.8 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Ataxia - adult onset v1.8 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Ataxia - adult onset v1.8 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.11 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Ataxia - adult onset v1.7 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Mendeliome v1.1670 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Repeat Disorders v0.158 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Marked gene: ZFHX3 as ready
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Gene: zfhx3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Classified gene: ZFHX3 as Green List (high evidence)
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Gene: zfhx3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2541 ZFHX3 Bryony Thompson gene: ZFHX3 was added
gene: ZFHX3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZFHX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFHX3 were set to 38508705
Phenotypes for gene: ZFHX3 were set to developmental and epileptic encephalopathy MONDO:0100062
Review for gene: ZFHX3 was set to GREEN
gene: ZFHX3 was marked as current diagnostic
Added comment: 8 unrelated probands with biallelic variants and a phenotype consistent with DEE and childhood partial epilepsy. Also a supporting Drosophila Zfh2 knockdown model with seizure-like behaviour.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Marked gene: GTF3C5 as ready
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Classified gene: GTF3C5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5756 GTF3C5 Bryony Thompson gene: GTF3C5 was added
gene: GTF3C5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
gene: GTF3C5 was marked as current diagnostic
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Mendeliome v1.1669 GTF3C5 Bryony Thompson Marked gene: GTF3C5 as ready
Mendeliome v1.1669 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Mendeliome v1.1669 GTF3C5 Bryony Thompson Classified gene: GTF3C5 as Green List (high evidence)
Mendeliome v1.1669 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Mendeliome v1.1668 GTF3C5 Bryony Thompson gene: GTF3C5 was added
gene: GTF3C5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Mendeliome v1.1667 MCOLN1 Zornitza Stark Phenotypes for gene: MCOLN1 were changed from Mucolipidosis IV, MIM# 252650; MONDO:0009653 to Mucolipidosis IV, MIM# 252650; MONDO:0009653; Lisch epithelial corneal dystrophy, OMIM# 620763
Mendeliome v1.1666 MCOLN1 Zornitza Stark Publications for gene: MCOLN1 were set to
Mendeliome v1.1665 MCOLN1 Zornitza Stark Mode of inheritance for gene: MCOLN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1664 MCOLN1 Zornitza Stark edited their review of gene: MCOLN1: Added comment: PMID 37972748: 23 affected individuals from 13 families with Lisch epithelial corneal dystrophy. WGS in 2 families and then targeted Sanger sequencing in the other families identified 9 rare heterozygous loss of function variants in MCOLN1. Homozygous and compound-heterozygous state of 4 of 9 LECD-associated variants cause Mucolipidosis IV (MLIV), which comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. Six parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype. Heterozygous MCOLN1 variants can be associated with incomplete penetrance and variable expressivity of LECD with an estimated penetrance of 0.2% for MCOLN1 loss-of-function variants based on gnomAD.; Changed publications: 37972748; Changed phenotypes: Mucolipidosis IV, MIM# 252650, MONDO:0009653, Lisch epithelial corneal dystrophy, OMIM# 620763; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Corneal Dystrophy v1.10 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Corneal Dystrophy v1.10 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Growth failure v1.75 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Growth failure v1.75 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5755 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Intellectual disability syndromic and non-syndromic v0.5755 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.257 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Microcephaly v1.257 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Mendeliome v1.1664 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Mendeliome v1.1664 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.10 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Deafness_IsolatedAndComplex v1.178 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Mendeliome v1.1664 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Intellectual disability syndromic and non-syndromic v0.5755 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Intellectual disability syndromic and non-syndromic v0.5754 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Intellectual disability syndromic and non-syndromic v0.5754 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.177 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Deafness_IsolatedAndComplex v1.177 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.9 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Amelogenesis imperfecta v1.9 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1663 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Mendeliome v1.1663 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.35 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from Andersen Tawil syndrome, LQTS to catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Catecholaminergic Polymorphic Ventricular Tachycardia v0.34 KCNJ2 Zornitza Stark Classified gene: KCNJ2 as Red List (low evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.34 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Marked gene: KCNB2 as ready
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Classified gene: KCNB2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2539 KCNB2 Zornitza Stark gene: KCNB2 was added
gene: KCNB2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to AMBER
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Fetal anomalies v1.230 FRYL Zornitza Stark Classified gene: FRYL as Green List (high evidence)
Fetal anomalies v1.230 FRYL Zornitza Stark Gene: fryl has been classified as Green List (High Evidence).
Fetal anomalies v1.229 FRYL Zornitza Stark reviewed gene: FRYL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, FRYL-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark Marked gene: TRPV5 as ready
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark Gene: trpv5 has been classified as Red List (Low Evidence).
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark gene: TRPV5 was added
gene: TRPV5 was added to Renal Tubulopathies and related disorders. Sources: Literature
Mode of inheritance for gene: TRPV5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV5 were set to 38528055; 14679186
Phenotypes for gene: TRPV5 were set to TRPV5-related hypercalciuria (MONDO:0009550)
Review for gene: TRPV5 was set to RED
Added comment: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.

PMID: 14679186
TRPV5 knockout mice model was used to assess whether the abolishment of TRPV5 led to a disruption in Ca2+ handling. The effects of the disruption in Ca2+ handling resulted in bone abnormalities in the mice and is likely the cause of idiopathic hypercalciuria.
Sources: Literature
Fetal anomalies v1.229 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly (MONDO:0016296), DISP1-related
Fetal anomalies v1.228 DISP1 Zornitza Stark Publications for gene: DISP1 were set to 27363716; 19184110; 26748417; 23542665
Fetal anomalies v1.227 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.226 DISP1 Zornitza Stark Classified gene: DISP1 as Green List (high evidence)
Fetal anomalies v1.226 DISP1 Zornitza Stark Gene: disp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.225 DISP1 Zornitza Stark edited their review of gene: DISP1: Added comment: PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.; Changed rating: GREEN; Changed publications: 19184110, 26748417, 23542665, 38529886; Changed phenotypes: Holoprosencephaly (MONDO:0016296), DISP1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5754 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly (MONDO:0016296), DISP1-related
Intellectual disability syndromic and non-syndromic v0.5753 DISP1 Zornitza Stark Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Intellectual disability syndromic and non-syndromic v0.5752 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5751 DISP1 Zornitza Stark Classified gene: DISP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5751 DISP1 Zornitza Stark Gene: disp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5750 DISP1 Zornitza Stark edited their review of gene: DISP1: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.5750 DISP1 Zornitza Stark edited their review of gene: DISP1: Added comment: PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.; Changed publications: 19184110, 26748417, 23542665, 38529886; Changed phenotypes: Holoprosencephaly (MONDO:0016296), DISP1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1663 DOCK4 Zornitza Stark Marked gene: DOCK4 as ready
Mendeliome v1.1663 DOCK4 Zornitza Stark Gene: dock4 has been classified as Green List (High Evidence).
Mendeliome v1.1663 DOCK4 Zornitza Stark Classified gene: DOCK4 as Green List (high evidence)
Mendeliome v1.1663 DOCK4 Zornitza Stark Gene: dock4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5750 DOCK4 Bryony Thompson Phenotypes for gene: DOCK4 were changed from to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Intellectual disability syndromic and non-syndromic v0.5749 DOCK4 Bryony Thompson Publications for gene: DOCK4 were set to
Holoprosencephaly and septo-optic dysplasia v1.14 DISP1 Bryony Thompson Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Intellectual disability syndromic and non-syndromic v0.5748 DOCK4 Bryony Thompson Mode of inheritance for gene: DOCK4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v1.13 DISP1 Bryony Thompson Mode of inheritance for gene: DISP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5747 DOCK4 Bryony Thompson Classified gene: DOCK4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5747 DOCK4 Bryony Thompson Gene: dock4 has been classified as Green List (High Evidence).
Mendeliome v1.1662 TRPV5 Bryony Thompson Marked gene: TRPV5 as ready
Mendeliome v1.1662 TRPV5 Bryony Thompson Gene: trpv5 has been classified as Red List (Low Evidence).
Mendeliome v1.1662 TRPV5 Bryony Thompson Publications for gene: TRPV5 were set to PMID: 38528055
Holoprosencephaly and septo-optic dysplasia v1.12 DISP1 Bryony Thompson Classified gene: DISP1 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v1.12 DISP1 Bryony Thompson Gene: disp1 has been classified as Green List (High Evidence).
Mendeliome v1.1661 TRPV5 Bryony Thompson Classified gene: TRPV5 as Red List (low evidence)
Mendeliome v1.1661 TRPV5 Bryony Thompson Gene: trpv5 has been classified as Red List (Low Evidence).
Mendeliome v1.1660 TRPV5 Sangavi Sivagnanasundram edited their review of gene: TRPV5: Changed publications: PMID: 38528055, 14679186
Mendeliome v1.1660 TRPV5 Sangavi Sivagnanasundram changed review comment from: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.
Sources: Other; to: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.

PMID: 14679186
TRPV5 knockout mice model was used to assess whether the abolishment of TRPV5 led to a disruption in Ca2+ handling. The effects of the disruption in Ca2+ handling resulted in bone abnormalities in the mice and is likely the cause of idiopathic hypercalciuria.

Sources: Other
Mendeliome v1.1660 DOCK4 Sangavi Sivagnanasundram gene: DOCK4 was added
gene: DOCK4 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DOCK4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DOCK4 were set to PMID: 38526744
Phenotypes for gene: DOCK4 were set to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Review for gene: DOCK4 was set to GREEN
Added comment: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5746 DOCK4 Sangavi Sivagnanasundram changed review comment from: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).; to: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Intellectual disability syndromic and non-syndromic v0.5746 DOCK4 Sangavi Sivagnanasundram changed review comment from: Well-established gene-disease association

7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).; to: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Mendeliome v1.1660 DISP1 Bryony Thompson Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Mendeliome v1.1659 DISP1 Bryony Thompson Mode of inheritance for gene: DISP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1658 DISP1 Bryony Thompson Classified gene: DISP1 as Green List (high evidence)
Mendeliome v1.1658 DISP1 Bryony Thompson Gene: disp1 has been classified as Green List (High Evidence).
Mendeliome v1.1657 DISP1 Sangavi Sivagnanasundram changed review comment from: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

; to: Gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

Mendeliome v1.1657 DISP1 Sangavi Sivagnanasundram changed review comment from: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).

Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function f DISP1 cause HPE as well.; to: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

Fetal anomalies v1.225 FRYL Ain Roesley Marked gene: FRYL as ready
Fetal anomalies v1.225 FRYL Ain Roesley Gene: fryl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.225 FRYL Ain Roesley Classified gene: FRYL as Amber List (moderate evidence)
Fetal anomalies v1.225 FRYL Ain Roesley Gene: fryl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.224 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to AMBER
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

7/14 with cardiac anomalies

Of interest to this panel: 1x tetralogy of fallot (TOF) with pulmonary atresia (PA), 2x dextrocardia, 1x hypoplastic left heart syndrome

Other reported features AVSD, VSD, PDA
Sources: Literature
Congenital Heart Defect v0.416 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Congenital Heart Defect v0.416 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Congenital Heart Defect v0.415 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Marked gene: FRYL as ready
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Mendeliome v1.1657 FRYL Ain Roesley Marked gene: FRYL as ready
Mendeliome v1.1657 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5745 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Mendeliome v1.1657 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Mendeliome v1.1657 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Mendeliome v1.1656 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Marked gene: KCNB2 as ready
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Classified gene: KCNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1655 KCNB2 Ain Roesley Marked gene: KCNB2 as ready
Mendeliome v1.1655 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5743 KCNB2 Ain Roesley gene: KCNB2 was added
gene: KCNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
gene: KCNB2 was marked as current diagnostic
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Sources: Literature
Mendeliome v1.1655 KCNB2 Ain Roesley Classified gene: KCNB2 as Green List (high evidence)
Mendeliome v1.1655 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1654 KCNB2 Ain Roesley changed review comment from: 7 individuals, all missense
1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature; to: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Mendeliome v1.1654 KCNB2 Ain Roesley gene: KCNB2 was added
gene: KCNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
gene: KCNB2 was marked as current diagnostic
Added comment: 7 individuals, all missense
1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5742 DOCK4 Sangavi Sivagnanasundram edited their review of gene: DOCK4: Changed rating: GREEN
Catecholaminergic Polymorphic Ventricular Tachycardia v0.33 KCNJ2 Sangavi Sivagnanasundram reviewed gene: KCNJ2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: catecholaminergic polymorphic ventricular tachycardia MONDO:0017990; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.223 MAP3K20 Zornitza Stark edited their review of gene: MAP3K20: Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.; Changed publications: 38451290; Changed phenotypes: Syndromic disease, MONDO:0002254, MAP3K20-related, Centronuclear myopathy 6 with fiber-type disproportion MIM#617760, Split-foot malformation with mesoaxial polydactyly MIM#616890; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.84 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Ectodermal Dysplasia. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.176 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Craniosynostosis v1.67 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Mendeliome v1.1653 MAP3K20 Zornitza Stark Phenotypes for gene: MAP3K20 were changed from Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890 to Syndromic disease, MONDO:0002254, MAP3K20-related; Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890
Mendeliome v1.1652 MAP3K20 Zornitza Stark Publications for gene: MAP3K20 were set to 27816943; 26755636
Mendeliome v1.1651 MAP3K20 Zornitza Stark Mode of inheritance for gene: MAP3K20 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1650 MAP3K20 Zornitza Stark reviewed gene: MAP3K20: Rating: GREEN; Mode of pathogenicity: None; Publications: 38451290; Phenotypes: Syndromic disease, MONDO:0002254, MAP3K20-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.257 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237; 38501757; 36739862
Microcephaly v1.256 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1650 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Mendeliome v1.1650 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Microcephaly v1.256 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Microcephaly v1.256 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Mendeliome v1.1649 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Mendeliome v1.1649 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Fetal anomalies v1.223 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1649 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Fetal anomalies v1.223 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Fetal anomalies v1.223 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Microcephaly v1.255 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.222 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1648 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Mendeliome v1.1647 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1647 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Mendeliome v1.1647 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Mendeliome v1.1646 SASS6 Ain Roesley Deleted their comment
Mendeliome v1.1646 SASS6 Ain Roesley commented on gene: SASS6: PMID: 38501757
1x compound het for a fs and +3 splice variant.

Using cDNA RT-ed from mother's RNA, exons 13-15 were amplified and exon 14 was found to be skipped resulting in c.1546_1674del and p.516_558del

PMID: 36739862
1x family, compound het for 2 missense
Functional studies not performed
Mendeliome v1.1646 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1646 FANCI Ain Roesley Phenotypes for gene: FANCI were changed from Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186 to Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186; primary ovarian failure MONDO:0005387, FANCI-related
Mendeliome v1.1645 FANCI Ain Roesley reviewed gene: FANCI: Rating: AMBER; Mode of pathogenicity: None; Publications: 38483614; Phenotypes: primary ovarian failure MONDO:0005387, FANCI-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley edited their review of gene: FANCI: Changed phenotypes: primary ovarian failure MONDO:0005387, FANCI-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Marked gene: FANCI as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Gene: fanci has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Classified gene: FANCI as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Gene: fanci has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.324 FANCI Ain Roesley gene: FANCI was added
gene: FANCI was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: FANCI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCI were set to 38483614
Review for gene: FANCI was set to AMBER
gene: FANCI was marked as current diagnostic
Added comment: WES however FANCI was specifically looked at based on KO mouse model which had premature exhaustion of primordial follicles leading to complete sterility.

2x compound hets: 2x missense + 1x canonical splice+1x missense

Minigene performed on the splice variant
Functional assays using KO cells + expression of variant demonstrated reduced ubiquitination of FANCI and increased DNA damage under replication stress
Sources: Literature
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Classified gene: MCOLN1 as Green List (high evidence)
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Gene: mcoln1 has been classified as Green List (High Evidence).
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Classified gene: MCOLN1 as Green List (high evidence)
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Gene: mcoln1 has been classified as Green List (High Evidence).
Corneal Dystrophy v1.9 MCOLN1 Chirag Patel gene: MCOLN1 was added
gene: MCOLN1 was added to Corneal Dystrophy. Sources: Literature
Mode of inheritance for gene: MCOLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCOLN1 were set to PMID: 37972748,
Phenotypes for gene: MCOLN1 were set to Lisch epithelial corneal dystrophy, OMIM# 620763
Review for gene: MCOLN1 was set to GREEN
gene: MCOLN1 was marked as current diagnostic
Added comment: 23 affected individuals from 13 families with Lisch epithelial corneal dystrophy. WGS in 2 families and then targeted Sanger sequencing in the other families identified 9 rare heterozygous loss of function variants in MCOLN1.

Homozygous and compound-heterozygous state of 4 of 9 LECD-associated variants cause Mucolipidosis IV (MLIV), which comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. Six parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype.

Heterozygous MCOLN1 variants can be associated with incomplete penetrance and variable expressivity of LECD with an estimated penetrance of 0.2% for MCOLN1 loss-of-function variants based on gnomAD.
Sources: Literature
Deafness_IsolatedAndComplex v1.175 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.175 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5742 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5742 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.9 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Amelogenesis imperfecta v1.9 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.174 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5741 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Amelogenesis imperfecta v1.8 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Amelogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.255 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephaly v1.255 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.254 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephaly v1.254 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Growth failure v1.75 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Growth failure v1.75 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5738 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Microcephaly v1.253 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Growth failure v1.74 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.28 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Microcephalic Primordial Dwarfism and Slender bone dysplasias. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Mendeliome v1.1645 CAPNS1 Zornitza Stark Marked gene: CAPNS1 as ready
Mendeliome v1.1645 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1645 CAPNS1 Zornitza Stark Classified gene: CAPNS1 as Amber List (moderate evidence)
Mendeliome v1.1645 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1644 CAPNS1 Zornitza Stark gene: CAPNS1 was added
gene: CAPNS1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CAPNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPNS1 were set to 38230350
Phenotypes for gene: CAPNS1 were set to Hereditary pulmonary arterial hypertension MONDO:0017148, CAPNS1-related
Review for gene: CAPNS1 was set to AMBER
Added comment: Three individuals from two families reported with homozygous splice site variants.
Sources: Expert list
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Marked gene: CAPNS1 as ready
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Classified gene: CAPNS1 as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.36 CAPNS1 Zornitza Stark gene: CAPNS1 was added
gene: CAPNS1 was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: CAPNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPNS1 were set to 38230350
Phenotypes for gene: CAPNS1 were set to Hereditary pulmonary arterial hypertension MONDO:0017148, CAPNS1-related
Review for gene: CAPNS1 was set to AMBER
Added comment: Three individuals from two families reported with homozygous splice site variants.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5737 USP27X Zornitza Stark Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984
Intellectual disability syndromic and non-syndromic v0.5736 USP27X Zornitza Stark Publications for gene: USP27X were set to 25644381
Intellectual disability syndromic and non-syndromic v0.5735 USP27X Zornitza Stark Classified gene: USP27X as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5735 USP27X Zornitza Stark Gene: usp27x has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5734 USP27X Zornitza Stark edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1643 USP27X Zornitza Stark Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1642 USP27X Zornitza Stark Publications for gene: USP27X were set to 25644381
Mendeliome v1.1641 USP27X Zornitza Stark Classified gene: USP27X as Green List (high evidence)
Mendeliome v1.1641 USP27X Zornitza Stark Gene: usp27x has been classified as Green List (High Evidence).
Mendeliome v1.1640 USP27X Zornitza Stark edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1640 ZNF143 Bryony Thompson Classified gene: ZNF143 as Amber List (moderate evidence)
Mendeliome v1.1640 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1639 ZNF143 Bryony Thompson reviewed gene: ZNF143: Rating: AMBER; Mode of pathogenicity: None; Publications: 27349184, 33845046, 9009278, 22268977, 27349184, 27349184; Phenotypes: methylmalonic aciduria and homocystinuria MONDO:0016826; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1639 TCN1 Bryony Thompson Marked gene: TCN1 as ready
Mendeliome v1.1639 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1639 TCN1 Bryony Thompson Classified gene: TCN1 as Amber List (moderate evidence)
Mendeliome v1.1639 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1638 TCN1 Bryony Thompson gene: TCN1 was added
gene: TCN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN1 were set to 29764838; 19686235
Phenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659
Review for gene: TCN1 was set to AMBER
Added comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease
Sources: Literature
Mendeliome v1.1637 FEM1B Zornitza Stark Classified gene: FEM1B as Green List (high evidence)
Mendeliome v1.1637 FEM1B Zornitza Stark Gene: fem1b has been classified as Green List (High Evidence).
Mendeliome v1.1636 FEM1B Zornitza Stark Publications for gene: FEM1B were set to PMID: 31036916
Mendeliome v1.1635 FEM1B Zornitza Stark Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5734 FEM1B Zornitza Stark Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5733 FEM1B Zornitza Stark Publications for gene: FEM1B were set to 31036916
Mendeliome v1.1634 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5732 FEM1B Zornitza Stark Classified gene: FEM1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5732 FEM1B Zornitza Stark Gene: fem1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5731 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Marked gene: USP14 as ready
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Classified gene: USP14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5730 USP14 Zornitza Stark Classified gene: USP14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5730 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5729 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793; 35066879
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to AMBER
Added comment: AMBER rating as two of the families had affected fetuses, one had a severely affected newborn, and fourth had a progressive course: none fit well with ID, though there's likely to be a continuum.

PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.

PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Mendeliome v1.1634 DISP1 Sangavi Sivagnanasundram reviewed gene: DISP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 38529886; Phenotypes: Holoprosencephaly (MONDO:0016296); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1634 TRPV5 Sangavi Sivagnanasundram gene: TRPV5 was added
gene: TRPV5 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: TRPV5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV5 were set to PMID: 38528055
Phenotypes for gene: TRPV5 were set to TRPV5-related hypercalciuria (MONDO:0009550)
Review for gene: TRPV5 was set to RED
Added comment: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5728 DOCK4 Sangavi Sivagnanasundram reviewed gene: DOCK4: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38526744; Phenotypes: DOCK4-related neurodevelopmental disorder (MONDO:0060490); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Metabolic Disorders Superpanel v8.125 Bryony Thompson Changed child panels to: Congenital Disorders of Glycosylation; Miscellaneous Metabolic Disorders; Calcium and Phosphate disorders; Fatty Acid Oxidation Defects; Hypertension and Aldosterone disorders; Lysosomal Storage Disorder; Neurotransmitter Defects; Disorders of branched chain amino acid metabolism; Glycogen Storage Diseases; Rhabdomyolysis and Metabolic Myopathy; Inherited vitamin B12 or cobalamin deficiency; Mitochondrial disease; Peroxisomal Disorders; Iron metabolism disorders; Dyslipidaemia; Vitamin C Pathway Disorders; Porphyria; Hyperammonaemia
Miscellaneous Metabolic Disorders v1.44 DPYD Bryony Thompson Tag pharmacogenomic tag was added to gene: DPYD.
Callosome v0.521 USP14 Zornitza Stark Publications for gene: USP14 were set to PMID: 35066879
Callosome v0.520 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Callosome v0.520 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Callosome v0.519 USP14 Zornitza Stark reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.222 USP14 Zornitza Stark Publications for gene: USP14 were set to PMID: 35066879
Fetal anomalies v1.221 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Fetal anomalies v1.221 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Fetal anomalies v1.220 USP14 Zornitza Stark reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1634 USP14 Zornitza Stark Marked gene: USP14 as ready
Mendeliome v1.1634 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Mendeliome v1.1634 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Mendeliome v1.1634 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Mendeliome v1.1633 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793; 35066879
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to GREEN
Added comment: PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.

PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Vitamin metabolism disorders v1.0 Bryony Thompson promoted panel to version 1.0
Miscellaneous Metabolic Disorders v1.44 Bryony Thompson removed gene:THAP11 from the panel
Miscellaneous Metabolic Disorders v1.43 Bryony Thompson removed gene:ZNF143 from the panel
Miscellaneous Metabolic Disorders v1.42 Bryony Thompson removed gene:TCN2 from the panel
Miscellaneous Metabolic Disorders v1.41 Bryony Thompson removed gene:MTR from the panel
Miscellaneous Metabolic Disorders v1.40 Bryony Thompson removed gene:MMADHC from the panel
Vitamin metabolism disorders v0.36 MMADHC Bryony Thompson Tag treatable tag was added to gene: MMADHC.
Miscellaneous Metabolic Disorders v1.39 Bryony Thompson removed gene:MMACHC from the panel
Vitamin metabolism disorders v0.36 MMACHC Bryony Thompson Tag treatable tag was added to gene: MMACHC.
Miscellaneous Metabolic Disorders v1.38 Bryony Thompson removed gene:LMBRD1 from the panel
Vitamin metabolism disorders v0.36 LMBRD1 Bryony Thompson Tag treatable tag was added to gene: LMBRD1.
Miscellaneous Metabolic Disorders v1.37 Bryony Thompson removed gene:HCFC1 from the panel
Miscellaneous Metabolic Disorders v1.36 Bryony Thompson removed gene:GIF from the panel
Miscellaneous Metabolic Disorders v1.35 Bryony Thompson removed gene:CUBN from the panel
Vitamin metabolism disorders v0.36 CUBN Bryony Thompson Tag treatable tag was added to gene: CUBN.
Miscellaneous Metabolic Disorders v1.34 CBS Bryony Thompson Phenotypes for gene: CBS were changed from Homocystinuria, B6-responsive and nonresponsive types MIM#236200; disorder of intracellular cobalamin metabolism to Homocystinuria, B6-responsive and nonresponsive types MIM#236200; disorder of intracellular cobalamin metabolism; metabolic disorder of sulfur metabolism
Miscellaneous Metabolic Disorders v1.33 Bryony Thompson removed gene:AMN from the panel
Miscellaneous Metabolic Disorders v1.32 Bryony Thompson removed gene:ABCD4 from the panel
Vitamin metabolism disorders v0.36 ABCD4 Bryony Thompson Phenotypes for gene: ABCD4 were changed from Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857 to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857; disorder of vitamin B12 metabolism
Vitamin metabolism disorders v0.35 Bryony Thompson Panel status changed from internal to public
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Marked gene: TCN1 as ready
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson changed review comment from: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels
Sources: Literature; to: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease
Sources: Literature
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson edited their review of gene: TCN1: Changed publications: 29764838, 19686235
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Classified gene: TCN1 as Amber List (moderate evidence)
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.33 TCN1 Bryony Thompson gene: TCN1 was added
gene: TCN1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN1 were set to 19686235
Phenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659
Review for gene: TCN1 was set to AMBER
Added comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5728 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Mendeliome v1.1632 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Mendeliome v1.1631 ZFX Zornitza Stark edited their review of gene: ZFX: Changed phenotypes: Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Marked gene: MTRR as ready
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Gene: mtrr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Classified gene: MTRR as Green List (high evidence)
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Gene: mtrr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Marked gene: MTR as ready
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Gene: mtr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Classified gene: MTR as Green List (high evidence)
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Gene: mtr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Marked gene: MMADHC as ready
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Gene: mmadhc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Classified gene: MMADHC as Green List (high evidence)
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Gene: mmadhc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Marked gene: MMACHC as ready
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Classified gene: MMACHC as Green List (high evidence)
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Marked gene: LMBRD1 as ready
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Gene: lmbrd1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Classified gene: LMBRD1 as Green List (high evidence)
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Gene: lmbrd1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Marked gene: HCFC1 as ready
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Gene: hcfc1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Classified gene: HCFC1 as Green List (high evidence)
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Gene: hcfc1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Marked gene: GIF as ready
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Gene: gif has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Classified gene: GIF as Green List (high evidence)
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Gene: gif has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Marked gene: CUBN as ready
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Gene: cubn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Classified gene: CUBN as Green List (high evidence)
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Gene: cubn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Marked gene: AMN as ready
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Gene: amn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Classified gene: AMN as Green List (high evidence)
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Gene: amn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Marked gene: ABCD4 as ready
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Gene: abcd4 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Classified gene: ABCD4 as Green List (high evidence)
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Gene: abcd4 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.21 THAP11 Bryony Thompson Marked gene: THAP11 as ready
Vitamin metabolism disorders v0.21 THAP11 Bryony Thompson Gene: thap11 has been classified as Red List (Low Evidence).
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Marked gene: TCN2 as ready
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Gene: tcn2 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Classified gene: TCN2 as Green List (high evidence)
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Gene: tcn2 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.20 MTRR Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MTR Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MMADHC Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MMACHC Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 LMBRD1 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 HCFC1 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 GIF Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 CUBN Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 AMN Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 ABCD4 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.19 TCN2 Bryony Thompson gene: TCN2 was added
gene: TCN2 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN2 were set to 19373259
Phenotypes for gene: TCN2 were set to Transcobalamin II deficiency, 275350
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Marked gene: ZNF143 as ready
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Classified gene: ZNF143 as Amber List (moderate evidence)
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.17 ZNF143 Bryony Thompson gene: ZNF143 was added
gene: ZNF143 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: ZNF143 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF143 were set to 27349184; 33845046; 9009278; 22268977; 27349184; 27349184
Phenotypes for gene: ZNF143 were set to methylmalonic aciduria and homocystinuria MONDO:0016826
Review for gene: ZNF143 was set to AMBER
Added comment: Only a single case with biallelic variants reported. However, given a Moderate gene-disease validity classification by the General Inborn Errors of Metabolism GCEP (assessed 05/03/2024). The gene-disease relationship is also supported by biochemical evidence, functional alteration assays, model systems, and rescue experiments
Sources: Literature
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Classified gene: THAP11 as Red List (low evidence)
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity classification on 09/02/2024 by General Inborn Errors of Metabolism GCEP
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Gene: thap11 has been classified as Red List (Low Evidence).
Vitamin metabolism disorders v0.15 THAP11 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.15 THAP11 Bryony Thompson gene: THAP11 was added
gene: THAP11 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: THAP11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THAP11 were set to 28449119
Phenotypes for gene: THAP11 were set to Methylmalonic aciduria and homocystinuria MONDO:0016826
Review for gene: THAP11 was set to RED
Added comment: Sources: Literature
Vitamin metabolism disorders v0.14 HCFC1 Bryony Thompson gene: HCFC1 was added
gene: HCFC1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: HCFC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HCFC1 were set to 24011988
Phenotypes for gene: HCFC1 were set to methylmalonic acidemia with homocystinuria, type cblX MONDO:0010657; disorder of cobalamin metabolism
Review for gene: HCFC1 was set to GREEN
gene: HCFC1 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.13 ABCD4 Bryony Thompson gene: ABCD4 was added
gene: ABCD4 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: ABCD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCD4 were set to 22922874; 31113616; 30651581; 28572511
Phenotypes for gene: ABCD4 were set to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857
Review for gene: ABCD4 was set to GREEN
gene: ABCD4 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.12 MTR Bryony Thompson gene: MTR was added
gene: MTR was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MTR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTR were set to 8968735; 27604308
Phenotypes for gene: MTR were set to Homocystinuria-megaloblastic anemia, cblG complementation type MIM#250940; Organic aciduria
Review for gene: MTR was set to GREEN
gene: MTR was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.11 LMBRD1 Bryony Thompson gene: LMBRD1 was added
gene: LMBRD1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: LMBRD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMBRD1 were set to 19136951; 27604308
Phenotypes for gene: LMBRD1 were set to Methylmalonic aciduria and homocystinuria, cblF type MIM#277380; Disorders of cobalamin absorption, transport and metabolism
Review for gene: LMBRD1 was set to GREEN
gene: LMBRD1 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.10 MTRR Bryony Thompson gene: MTRR was added
gene: MTRR was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MTRR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTRR were set to 27604308; 9501215
Phenotypes for gene: MTRR were set to Homocystinuria-megaloblastic anemia, cbl E type MIM#236270; Disorders of the metabolism of sulphur amino acids
Review for gene: MTRR was set to GREEN
gene: MTRR was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.9 MMADHC Bryony Thompson gene: MMADHC was added
gene: MMADHC was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMADHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMADHC were set to 27604308; 18385497
Phenotypes for gene: MMADHC were set to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410; Disorders of cobalamin absorption, transport and metabolism
Review for gene: MMADHC was set to GREEN
gene: MMADHC was marked as current diagnostic
Added comment: Sources: Literature
Mendeliome v1.1631 PRDX1 Bryony Thompson Marked gene: PRDX1 as ready
Mendeliome v1.1631 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Mendeliome v1.1631 PRDX1 Bryony Thompson Classified gene: PRDX1 as Green List (high evidence)
Mendeliome v1.1631 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Mendeliome v1.1630 PRDX1 Bryony Thompson gene: PRDX1 was added
gene: PRDX1 was added to Mendeliome. Sources: Literature
digenic tags were added to gene: PRDX1.
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to 29302025; 35190856
Phenotypes for gene: PRDX1 were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184
Mode of pathogenicity for gene: PRDX1 was set to Other
Review for gene: PRDX1 was set to GREEN
Added comment: Only variants affecting the canonical splice acceptor site of intron 5 (e.g. c.515-1G-T, c.515-2A-T) that cause skipping of exon 6 and the polyA termination signal of PRDX1 produce an MMACHC epimutation. The resulting read-through transcript extends through the adjacent MMACHC locus in the antisense orientation. These PRDX1 exon 6 acceptor splice site variants cause disease through digenic inheritance with a pathogenic MMACHC on the other allele.
Sources: Literature
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Marked gene: PRDX1 as ready
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Classified gene: PRDX1 as Green List (high evidence)
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.7 PRDX1 Bryony Thompson Tag digenic tag was added to gene: PRDX1.
Vitamin metabolism disorders v0.7 PRDX1 Bryony Thompson gene: PRDX1 was added
gene: PRDX1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to 29302025; 35190856
Phenotypes for gene: PRDX1 were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184
Mode of pathogenicity for gene: PRDX1 was set to Other
Review for gene: PRDX1 was set to GREEN
Added comment: Only variants affecting the canonical splice acceptor site of intron 5 (e.g. c.515-1G-T, c.515-2A-T) that cause skipping of exon 6 and the polyA termination signal of PRDX1 produce an MMACHC epimutation. The resulting read-through transcript extends through the adjacent MMACHC locus in the antisense orientation. These PRDX1 exon 6 acceptor splice site variants cause disease through digenic inheritance with a pathogenic MMACHC on the other allele.
Sources: Literature
Vitamin metabolism disorders v0.6 MMACHC Bryony Thompson gene: MMACHC was added
gene: MMACHC was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to 27604308; 16311595
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400; Disorders of cobalamin absorption, transport and metabolism
Review for gene: MMACHC was set to GREEN
gene: MMACHC was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Marked gene: MMAB as ready
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Gene: mmab has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Classified gene: MMAB as Green List (high evidence)
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Gene: mmab has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.4 MMAB Bryony Thompson gene: MMAB was added
gene: MMAB was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMAB were set to 12471062; 20556797; 35712814; 24813872
Phenotypes for gene: MMAB were set to methylmalonic aciduria, cblB type MONDO:0009614
Review for gene: MMAB was set to GREEN
gene: MMAB was marked as current diagnostic
Added comment: Well-established gene-disease association. Inborn error of cobalamin metabolism.
Sources: Literature
Vitamin metabolism disorders v0.3 AMN Bryony Thompson gene: AMN was added
gene: AMN was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: AMN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMN were set to 12590260; 27604308
Phenotypes for gene: AMN were set to Imerslund-Grasbeck syndrome 2 MIM#618882; Disorders of cobalamin absorption, transport and metabolism
Review for gene: AMN was set to GREEN
gene: AMN was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.2 CUBN Bryony Thompson gene: CUBN was added
gene: CUBN was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: CUBN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CUBN were set to 10080186; 31613795
Phenotypes for gene: CUBN were set to Proteinuria, chronic benign MIM#618884; Imerslund-Grasbeck syndrome 1 MIM#261100; Intrinsic factor receptor deficiency due to CUBN mutations (Disorders of cobalamin absorption, transport and metabolism)
Review for gene: CUBN was set to GREEN
Added comment: Sources: Literature
Mendeliome v1.1629 PSMB10 Zornitza Stark Phenotypes for gene: PSMB10 were changed from Proteasome-associated autoinflammatory syndrome 5, MIM# 619175 to Proteasome-associated autoinflammatory syndrome 5, MIM# 619175; Severe combined immunodeficiency, MONDO:0015974, PSMB10-related
Mendeliome v1.1628 PSMB10 Zornitza Stark Publications for gene: PSMB10 were set to 31783057; 37600812
Mendeliome v1.1627 PSMB10 Zornitza Stark Mode of inheritance for gene: PSMB10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1626 PSMB10 Zornitza Stark edited their review of gene: PSMB10: Added comment: PMID 38503300: Six individuals with three de novo missense variants. Individuals presented with T-B-NK± severe combined immunodeficiency (SCID) and clinical features suggestive of Omenn syndrome, including diarrhea, alopecia, and desquamating erythematous rash.; Changed publications: 31783057, 37600812, 38503300; Changed phenotypes: Proteasome-associated autoinflammatory syndrome 5, MIM# 619175, Severe combined immunodeficiency, MONDO:0015974, PSMB10-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 PSMB10 Zornitza Stark Marked gene: PSMB10 as ready
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 PSMB10 Zornitza Stark Classified gene: PSMB10 as Green List (high evidence)
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T absent B cells) v1.6 PSMB10 Zornitza Stark gene: PSMB10 was added
gene: PSMB10 was added to Severe Combined Immunodeficiency (absent T absent B cells). Sources: Literature
Mode of inheritance for gene: PSMB10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMB10 were set to 38503300
Phenotypes for gene: PSMB10 were set to Severe combined immunodeficiency, MONDO:0015974, PSMB10-related
Review for gene: PSMB10 was set to GREEN
Added comment: Six individuals with three de novo missense variants. Individuals presented with T-B-NK± severe combined immunodeficiency (SCID) and clinical features suggestive of Omenn syndrome, including diarrhea, alopecia, and desquamating erythematous rash.
Sources: Literature
Vitamin metabolism disorders v0.1 GIF Bryony Thompson gene: GIF was added
gene: GIF was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
new gene name tags were added to gene: GIF.
Mode of inheritance for gene: GIF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIF were set to 27604308; 14695536; 14576042
Phenotypes for gene: GIF were set to Intrinsic factor deficiency MIM#261000; Disorders of cobalamin absorption, transport and metabolism
Review for gene: GIF was set to GREEN
gene: GIF was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.0 Bryony Thompson Added Panel Inherited vitamin B12 or cobalamin deficiency
Set list of related panels to Abnormality of vitamin B12 metabolism; HP:0004341
Set panel types to: Royal Melbourne Hospital; Rare Disease
Transplant Co-Morbidity Superpanel v0.18 Bryony Thompson removed gene:IFNL3 from the panel
Leukodystrophy - adult onset v0.137 PRNP Bryony Thompson Marked gene: PRNP as ready
Leukodystrophy - adult onset v0.137 PRNP Bryony Thompson Gene: prnp has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.137 PRNP Bryony Thompson Classified gene: PRNP as Green List (high evidence)
Leukodystrophy - adult onset v0.137 PRNP Bryony Thompson Gene: prnp has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.136 PRNP Bryony Thompson gene: PRNP was added
gene: PRNP was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: PRNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRNP were set to 25220284; 24252267
Phenotypes for gene: PRNP were set to fatal familial insomnia MONDO:0010808
Mode of pathogenicity for gene: PRNP was set to Other
Review for gene: PRNP was set to GREEN
gene: PRNP was marked as current diagnostic
Added comment: White-matter abnormalities have been reported in inherited prion diseases
Sources: Other
Leukodystrophy - adult onset v0.135 ITM2B Bryony Thompson Marked gene: ITM2B as ready
Leukodystrophy - adult onset v0.135 ITM2B Bryony Thompson Gene: itm2b has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.135 ITM2B Bryony Thompson Classified gene: ITM2B as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.135 ITM2B Bryony Thompson Gene: itm2b has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.134 ITM2B Bryony Thompson gene: ITM2B was added
gene: ITM2B was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: ITM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITM2B were set to 10775542
Phenotypes for gene: ITM2B were set to ABri amyloidosis MONDO:0008306
Mode of pathogenicity for gene: ITM2B was set to Other
Review for gene: ITM2B was set to AMBER
Added comment: White matter abnormalities have been reported in 11 at-risk individuals from the original large family reported.
Sources: Other
Mendeliome v1.1626 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Mendeliome v1.1626 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Mendeliome v1.1625 CST3 Bryony Thompson reviewed gene: CST3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 38489591; Phenotypes: leukodystrophy MONDO:0019046, CST3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Marked gene: CST3 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.56 CST3 Bryony Thompson gene: CST3 was added
gene: CST3 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: CST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CST3 were set to 38489591
Phenotypes for gene: CST3 were set to leukodystrophy MONDO:0019046, CST3-related
Mode of pathogenicity for gene: CST3 was set to Other
Review for gene: CST3 was set to GREEN
Added comment: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. Suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.
Sources: Literature
Early-onset Dementia v1.12 CST3 Bryony Thompson Phenotypes for gene: CST3 were changed from Cerebral amyloid angiopathy MIM#105150 to Cerebral amyloid angiopathy MIM#105150; leukodystrophy MONDO:0019046
Early-onset Dementia v1.11 CST3 Bryony Thompson Publications for gene: CST3 were set to 22435454; 8866434; 2602413; 8108423
Early-onset Dementia v1.10 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Early-onset Dementia v1.10 CST3 Bryony Thompson Added comment: Comment on list classification: Cognitive decline is a feature of CST3-leukodystrophy
Early-onset Dementia v1.10 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Early-onset Dementia v1.9 CST3 Bryony Thompson edited their review of gene: CST3: Added comment: New gene-disease association: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. Suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.; Changed publications: 22435454, 8866434, 2602413, 8108423, 38489591; Changed phenotypes: Cerebral amyloid angiopathy MIM#105150, leukodystrophy MONDO:0019046
Leukodystrophy - adult onset v0.133 CST3 Bryony Thompson Marked gene: CST3 as ready
Leukodystrophy - adult onset v0.133 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.133 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Leukodystrophy - adult onset v0.133 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.132 CST3 Bryony Thompson gene: CST3 was added
gene: CST3 was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for gene: CST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CST3 were set to 38489591
Phenotypes for gene: CST3 were set to leukodystrophy MONDO:0019046
Review for gene: CST3 was set to GREEN
Added comment: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. The suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5727 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Intellectual disability syndromic and non-syndromic v0.5726 SLC32A1 Zornitza Stark reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 114, MIM# 620774; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2538 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Genetic Epilepsy v0.2537 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755, Developmental and epileptic encephalopathy 114, MIM# 620774
Mendeliome v1.1625 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Mendeliome v1.1624 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755, Developmental and epileptic encephalopathy 114, MIM# 620774
Intellectual disability syndromic and non-syndromic v0.5726 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Neurodevelopmental disorder (MONDO:0700092), CRELD1-related to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Intellectual disability syndromic and non-syndromic v0.5725 CRELD1 Zornitza Stark reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2537 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Genetic Epilepsy v0.2536 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Changed phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Mendeliome v1.1624 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Mendeliome v1.1623 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Changed phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771, Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Leukodystrophy - adult onset v0.131 FTDALS Bryony Thompson Classified STR: FTDALS as Green List (high evidence)
Leukodystrophy - adult onset v0.131 FTDALS Bryony Thompson Str: ftdals has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.130 FTDALS Bryony Thompson STR: FTDALS was added
STR: FTDALS was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for STR: FTDALS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FTDALS were set to 36970046; 36632182
Phenotypes for STR: FTDALS were set to frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105
Penetrance for STR: FTDALS were set to Incomplete
Review for STR: FTDALS was set to GREEN
STR: FTDALS was marked as clinically relevant
STR: FTDALS was marked as current diagnostic
Added comment: Expansion carriers showed widespread white-matter abnormalities in the brain
Sources: Literature
Leukodystrophy - adult onset v0.129 MAPT Bryony Thompson Marked gene: MAPT as ready
Leukodystrophy - adult onset v0.129 MAPT Bryony Thompson Gene: mapt has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.129 MAPT Bryony Thompson Classified gene: MAPT as Green List (high evidence)
Leukodystrophy - adult onset v0.129 MAPT Bryony Thompson Gene: mapt has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.128 MAPT Bryony Thompson gene: MAPT was added
gene: MAPT was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for gene: MAPT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPT were set to 33802612; 36970046
Phenotypes for gene: MAPT were set to semantic dementia MONDO:0010857
Mode of pathogenicity for gene: MAPT was set to Other
Review for gene: MAPT was set to GREEN
gene: MAPT was marked as current diagnostic
Added comment: White-matter abnormalities have been reported in symptomatic and pre-symptomatic carriers of MAPT pathogenic variants.
Sources: Literature
Leukodystrophy - adult onset v0.127 GRN Bryony Thompson Marked gene: GRN as ready
Leukodystrophy - adult onset v0.127 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.127 GRN Bryony Thompson Classified gene: GRN as Green List (high evidence)
Leukodystrophy - adult onset v0.127 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.126 GRN Bryony Thompson gene: GRN was added
gene: GRN was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: GRN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRN were set to 36970046; 36632182
Phenotypes for gene: GRN were set to GRN-related frontotemporal lobar degeneration with Tdp43 inclusions MONDO:0011842
Review for gene: GRN was set to GREEN
gene: GRN was marked as current diagnostic
Added comment: White matter abnormalities have been reported in presymptomatic carriers and affected carriers.
Sources: Other
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Marked gene: EHHADH as ready
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Gene: ehhadh has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Classified gene: EHHADH as Green List (high evidence)
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Gene: ehhadh has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.125 PSEN2 Bryony Thompson Marked gene: PSEN2 as ready
Leukodystrophy - adult onset v0.125 PSEN2 Bryony Thompson Gene: psen2 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.125 PSEN2 Bryony Thompson Classified gene: PSEN2 as Green List (high evidence)
Leukodystrophy - adult onset v0.125 PSEN2 Bryony Thompson Gene: psen2 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.124 PSEN2 Bryony Thompson gene: PSEN2 was added
gene: PSEN2 was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: PSEN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSEN2 were set to 36845656
Phenotypes for gene: PSEN2 were set to early-onset autosomal dominant Alzheimer disease MONDO:0015140
Mode of pathogenicity for gene: PSEN2 was set to Other
Review for gene: PSEN2 was set to GREEN
gene: PSEN2 was marked as current diagnostic
Added comment: White matter abnormalities are a common feature of Alzheimer's disease
Sources: Other
Early-onset Dementia v1.9 APP Bryony Thompson Marked gene: APP as ready
Early-onset Dementia v1.9 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Early-onset Dementia v1.9 APP Bryony Thompson Mode of pathogenicity for gene: APP was changed from to Other
Leukodystrophy - adult onset v0.123 PSEN1 Bryony Thompson Marked gene: PSEN1 as ready
Leukodystrophy - adult onset v0.123 PSEN1 Bryony Thompson Gene: psen1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.123 PSEN1 Bryony Thompson Classified gene: PSEN1 as Green List (high evidence)
Leukodystrophy - adult onset v0.123 PSEN1 Bryony Thompson Gene: psen1 has been classified as Green List (High Evidence).
Early-onset Dementia v1.8 APP Bryony Thompson Publications for gene: APP were set to
Leukodystrophy - adult onset v0.122 PSEN1 Bryony Thompson gene: PSEN1 was added
gene: PSEN1 was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: PSEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSEN1 were set to 36845656
Phenotypes for gene: PSEN1 were set to early-onset autosomal dominant Alzheimer disease MONDO:0015140
Mode of pathogenicity for gene: PSEN1 was set to Other
Review for gene: PSEN1 was set to GREEN
gene: PSEN1 was marked as current diagnostic
Added comment: White matter abnormalities are a common feature of Alzheimer's disease
Sources: Other
Leukodystrophy - adult onset v0.121 APP Bryony Thompson Marked gene: APP as ready
Leukodystrophy - adult onset v0.121 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.121 APP Bryony Thompson Classified gene: APP as Green List (high evidence)
Leukodystrophy - adult onset v0.121 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.120 APP Bryony Thompson gene: APP was added
gene: APP was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: APP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APP were set to 36845656
Phenotypes for gene: APP were set to early-onset autosomal dominant Alzheimer disease MONDO:0015140
Review for gene: APP was set to GREEN
gene: APP was marked as current diagnostic
Added comment: White matter abnormalities are a common feature of Alzheimer's disease
Sources: Other
Early-onset Dementia v1.7 APP Bryony Thompson Phenotypes for gene: APP were changed from to Alzheimer disease MONDO:0007088
Early-onset Dementia v1.6 APP Bryony Thompson Mode of inheritance for gene: APP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Marked gene: NRAS as ready
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Gene: nras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Classified gene: NRAS as Green List (high evidence)
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Gene: nras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.21 NRAS Bryony Thompson gene: NRAS was added
gene: NRAS was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: NRAS was set to Other
Publications for gene: NRAS were set to 24006476; 35999193; 32157705; 27900779
Phenotypes for gene: NRAS were set to Costello syndrome MONDO:0009026
Mode of pathogenicity for gene: NRAS was set to Other
Review for gene: NRAS was set to GREEN
gene: NRAS was marked as current diagnostic
Added comment: 5 cases with cutaneous skeletal hypophosphatemia syndrome and all with somatic mosaic activating NRAS Q61R
Sources: Literature
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Marked gene: HRAS as ready
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Gene: hras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Classified gene: HRAS as Green List (high evidence)
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Gene: hras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.19 HRAS Bryony Thompson gene: HRAS was added
gene: HRAS was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: HRAS was set to Other
Publications for gene: HRAS were set to 35738466; 36943390; 30373874; 27444071
Phenotypes for gene: HRAS were set to Costello syndrome MONDO:0009026
Mode of pathogenicity for gene: HRAS was set to Other
Review for gene: HRAS was set to GREEN
gene: HRAS was marked as current diagnostic
Added comment: Gain of function is the mechanism of disease and only somatic mosaic variants have been reported in association with hypophosphataemia
PMID: 35738466 - 1 case with a VUS & vitamin dependent rickets as a feature of the phenotype
PMID: 36943390 - mouse model with hypophosphataemia
PMID: 30373874 - 1 somatic mosaic HRAS c.182A>G (p.Gln61Arg) case with cutaneous skeletal hypophosphatemia syndrome (CSHS)
PMID: 27444071 - review with 4 cases of CSHS with somatic mosaic variants (G13R or Q61R)
Sources: Literature
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson Marked gene: ATP6V0A4 as ready
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson Gene: atp6v0a4 has been classified as Red List (Low Evidence).
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson gene: ATP6V0A4 was added
gene: ATP6V0A4 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: ATP6V0A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V0A4 were set to 35738466
Phenotypes for gene: ATP6V0A4 were set to renal tubular acidosis, distal, 3, with or without sensorineural hearing loss MONDO:0011268
Review for gene: ATP6V0A4 was set to RED
Added comment: 1 homozygous case with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Marked gene: ATP6V1B1 as ready
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Gene: atp6v1b1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Classified gene: ATP6V1B1 as Green List (high evidence)
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Gene: atp6v1b1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.16 ATP6V1B1 Bryony Thompson gene: ATP6V1B1 was added
gene: ATP6V1B1 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: ATP6V1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1B1 were set to 35738466; 18386070
Phenotypes for gene: ATP6V1B1 were set to renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss MONDO:0009968
Review for gene: ATP6V1B1 was set to GREEN
gene: ATP6V1B1 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of the condition
PMID: 35738466 - 2 homozygous & 1 Chet case with hypophosphataemic rickets and renal tubular dysfunction
PMID: 18386070 - 2 siblings with distal renal tubular acidosis and hypophosphataemic rickets homozygous for a missense variant (c.242T>C p.Leu81Pro)
Sources: Literature
Calcium and Phosphate disorders v1.10 EHHADH Bryony Thompson gene: EHHADH was added
gene: EHHADH was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: EHHADH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHHADH were set to 24401050; 35738466; 38310177
Phenotypes for gene: EHHADH were set to Fanconi renotubular syndrome 3 MONDO:0014275
Review for gene: EHHADH was set to GREEN
Added comment: Now 3 different variants from 4 families/cases were reported with consistent phenotypes. Assessed as Limited by ClinGen in March 2023. However, this assessment doesn't include: PMID: 35738466, 38310177; https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf
Additional info:
PMID: 35738466 - 1 family (proband and mother) with missense (c.385C>G, p.Leu129Val) with hypophosphataemic rickets and renal tubular dysfunction
PMID: 38310177 - case with a diagnosis of Fanconi renotubular syndrome with a whole gene deletion. Hypophosphataemic rickets was part of the clinical presentation
Sources: Literature
Calcium and Phosphate disorders v1.10 EHHADH Bryony Thompson gene: EHHADH was added
gene: EHHADH was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: EHHADH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHHADH were set to 24401050; 35738466; 38310177
Phenotypes for gene: EHHADH were set to Fanconi renotubular syndrome 3 MONDO:0014275
Review for gene: EHHADH was set to GREEN
Added comment: Now 3 different variants from 4 families/cases were reported with consistent phenotypes. Assessed as Limited by ClinGen in March 2023. However, this assessment doesn't include: PMID: 35738466, 38310177; https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf
Additional info:
PMID: 35738466 - 1 family (proband and mother) with missense (c.385C>G, p.Leu129Val) with hypophosphataemic rickets and renal tubular dysfunction
PMID: 38310177 - case with a diagnosis of Fanconi renotubular syndrome with a whole gene deletion. Hypophosphataemic rickets was part of the clinical presentation
Sources: Literature
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Marked gene: EHHADH as ready
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Publications for gene: EHHADH were set to 24401050
Renal Tubulopathies and related disorders v1.10 EHHADH Bryony Thompson Classified gene: EHHADH as Green List (high evidence)
Renal Tubulopathies and related disorders v1.10 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.9 EHHADH Bryony Thompson reviewed gene: EHHADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24401050, 35738466, 38310177; Phenotypes: Fanconi renotubular syndrome 3 MONDO:0014275; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1623 EHHADH Bryony Thompson Publications for gene: EHHADH were set to 24401050
Mendeliome v1.1622 EHHADH Bryony Thompson Classified gene: EHHADH as Green List (high evidence)
Mendeliome v1.1622 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Mendeliome v1.1621 EHHADH Bryony Thompson reviewed gene: EHHADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 35738466, 38310177, 24401050; Phenotypes: Fanconi renotubular syndrome 3 MONDO:0014275; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Marked gene: FGFR1 as ready
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Gene: fgfr1 has been classified as Amber List (Moderate Evidence).
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Classified gene: FGFR1 as Amber List (moderate evidence)
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Gene: fgfr1 has been classified as Amber List (Moderate Evidence).
Calcium and Phosphate disorders v1.8 FGFR1 Bryony Thompson gene: FGFR1 was added
gene: FGFR1 was added to Calcium and Phosphate disorders. Sources: Other
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR1 were set to 35738466; 36999651; 29147600; 26839958
Phenotypes for gene: FGFR1 were set to osteoglophonic dwarfism MONDO:0008150
Review for gene: FGFR1 was set to AMBER
gene: FGFR1 was marked as current diagnostic
Added comment: PMID: 35738466 - 1 case with vitamin dependent rickets & osteoglophonic dysplasia
PMID: 36999651 - 1 missense (VUS) in a case with hypophosphataemia
PMID: 29147600 - 1 case with Osteoglophonic dysplasia including hypophosphataemia, with c.1115G > A [p.(Cys372Tyr)]
PMID: 26839958 - mouse model demonstrates role for Fgrf1 in phosphate transport
Sources: Other
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Marked gene: INPPL1 as ready
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Gene: inppl1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Classified gene: INPPL1 as Green List (high evidence)
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Gene: inppl1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.6 INPPL1 Bryony Thompson gene: INPPL1 was added
gene: INPPL1 was added to Calcium and Phosphate disorders. Sources: Other
Mode of inheritance for gene: INPPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPPL1 were set to 23273567
Phenotypes for gene: INPPL1 were set to opsismodysplasia MONDO:0009785
Review for gene: INPPL1 was set to GREEN
gene: INPPL1 was marked as current diagnostic
Added comment: Hypophosphataemia can be a feature of the condition and has been reported in at least 5 individuals with chet/homozygous variants from 4 families.
Sources: Other
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Marked gene: SLC4A1 as ready
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Gene: slc4a1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson changed review comment from: Hypophosphataemic rickets can be a feature of condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature; to: Hypophosphataemic rickets can be a feature of the condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson edited their review of gene: SLC4A1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Mode of inheritance for gene: SLC4A1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson edited their review of gene: SLC4A1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson Classified gene: SLC4A1 as Green List (high evidence)
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson Gene: slc4a1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.3 SLC4A1 Bryony Thompson gene: SLC4A1 was added
gene: SLC4A1 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SLC4A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SLC4A1 were set to 35738466
Phenotypes for gene: SLC4A1 were set to renal tubular acidosis, distal, 4, with hemolytic anemia MONDO:0012700
Review for gene: SLC4A1 was set to GREEN
gene: SLC4A1 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Marked gene: SLC2A2 as ready
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Gene: slc2a2 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Classified gene: SLC2A2 as Green List (high evidence)
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Gene: slc2a2 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.1 SLC2A2 Bryony Thompson gene: SLC2A2 was added
gene: SLC2A2 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SLC2A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC2A2 were set to 35738466
Phenotypes for gene: SLC2A2 were set to glycogen storage disease due to GLUT2 deficiency MONDO:0009216
Review for gene: SLC2A2 was set to GREEN
gene: SLC2A2 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of the condition.
PMID: 35738466 - 4 homozygous & 1 Chet case with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Mendeliome v1.1621 RXFP2 Katie Ayers reviewed gene: RXFP2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 37208861, 38430325; Phenotypes: Infertility, cryptorchidism, non-obstructive azoospermia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.293 RXFP2 Katie Ayers edited their review of gene: RXFP2: Added comment: One individual with bilateral cryptorchidism and infertility had homozygous c.1406delT in RXFP2 (NM_130806.5), leading to a frameshift p.(Phe469Serfs*8). From consanguinous family.

Two affected brothers with homozygous missense variant c.1015A>G in RXFP2 (NM_130806.5) resulting in an amino acid substitution p.(Asn339Asp) with bilateral cryptorchidism.; Changed publications: 37208861; Changed phenotypes: Infertility, cryptorchidism, non-obstructive azoospermia
Differences of Sex Development v0.293 RXFP2 Katie Ayers edited their review of gene: RXFP2: Added comment: Homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing . NM_130806: c.1376-12A > G; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications: 38430325; Changed phenotypes: cryptorchidism and non-obstructive azoospermia; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.293 RXFP2 Katie Ayers commented on gene: RXFP2
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Marked gene: NDUFAF5 as ready
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Phenotypes for gene: NDUFAF5 were changed from to Mitochondrial complex I deficiency, nuclear type 3 MIM#618224
Genetic Epilepsy v0.2535 NDUFAF5 Zornitza Stark Publications for gene: NDUFAF5 were set to
Genetic Epilepsy v0.2534 NDUFAF5 Zornitza Stark Mode of inheritance for gene: NDUFAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2533 NDUFAF5 Zornitza Stark reviewed gene: NDUFAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Genetic Epilepsy v0.2532 NDUFA1 Zornitza Stark Publications for gene: NDUFA1 were set to
Genetic Epilepsy v0.2531 NDUFA1 Zornitza Stark Mode of inheritance for gene: NDUFA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2530 NDUFA1 Zornitza Stark reviewed gene: NDUFA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Marked gene: NDE1 as ready
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Gene: nde1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Phenotypes for gene: NDE1 were changed from to Microhydranencephaly 605013; Lissencephaly 4 (with microcephaly) 614019
Genetic Epilepsy v0.2529 NDE1 Zornitza Stark Publications for gene: NDE1 were set to
Genetic Epilepsy v0.2528 NDE1 Zornitza Stark Mode of inheritance for gene: NDE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Marked gene: NAGA as ready
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Gene: naga has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Phenotypes for gene: NAGA were changed from to Schindler disease, type I and type II 609241
Genetic Epilepsy v0.2526 NAGA Zornitza Stark Publications for gene: NAGA were set to
Genetic Epilepsy v0.2525 NAGA Zornitza Stark Mode of inheritance for gene: NAGA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2524 NAGA Zornitza Stark Classified gene: NAGA as Amber List (moderate evidence)
Genetic Epilepsy v0.2524 NAGA Zornitza Stark Gene: naga has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2523 NAGA Zornitza Stark edited their review of gene: NAGA: Changed rating: AMBER
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Marked gene: MTOR as ready
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Gene: mtor has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Phenotypes for gene: MTOR were changed from to Smith-Kingsmore syndrome, MIM# 616638; Focal cortical dysplasia, type II, somatic, MIM# 607341; Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Genetic Epilepsy v0.2522 MTOR Zornitza Stark Mode of pathogenicity for gene: MTOR was changed from to Other
Genetic Epilepsy v0.2521 MTOR Zornitza Stark Publications for gene: MTOR were set to
Genetic Epilepsy v0.2520 MTOR Zornitza Stark Mode of inheritance for gene: MTOR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from Homocystinuria due to MTHFR deficiency MIM#236250 to Homocystinuria due to MTHFR deficiency MIM#236250
Genetic Epilepsy v0.2518 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from to Homocystinuria due to MTHFR deficiency MIM#236250
Genetic Epilepsy v0.2517 MTHFR Zornitza Stark Publications for gene: MTHFR were set to
Genetic Epilepsy v0.2516 MTHFR Zornitza Stark Mode of inheritance for gene: MTHFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2515 MTHFR Zornitza Stark reviewed gene: MTHFR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Homocystinuria due to MTHFR deficiency MIM#236250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2515 MOCS2 Zornitza Stark Mode of inheritance for gene: MOCS2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2514 MOCS2 Zornitza Stark Mode of inheritance for gene: MOCS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2513 MOCS2 Zornitza Stark reviewed gene: MOCS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency B MIM#252160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Marked gene: MMADHC as ready
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Gene: mmadhc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Phenotypes for gene: MMADHC were changed from to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Publications for gene: MMADHC were set to
Genetic Epilepsy v0.2512 MMADHC Zornitza Stark Mode of inheritance for gene: MMADHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400
Genetic Epilepsy v0.2510 MMACHC Zornitza Stark Publications for gene: MMACHC were set to
Genetic Epilepsy v0.2509 MMACHC Zornitza Stark Mode of inheritance for gene: MMACHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Phenotypes for gene: MLC1 were changed from to Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004)
Genetic Epilepsy v0.2507 MLC1 Zornitza Stark Publications for gene: MLC1 were set to
Genetic Epilepsy v0.2506 MLC1 Zornitza Stark Mode of inheritance for gene: MLC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2505 MFF Zornitza Stark Marked gene: MFF as ready
Genetic Epilepsy v0.2505 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2505 MFF Zornitza Stark Phenotypes for gene: MFF were changed from to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086
Genetic Epilepsy v0.2504 MFF Zornitza Stark Publications for gene: MFF were set to
Genetic Epilepsy v0.2503 MFF Zornitza Stark Mode of inheritance for gene: MFF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1621 KAT6B Ain Roesley Phenotypes for gene: KAT6B were changed from SBBYSS syndrome MIM#603736; Genitopatellar syndrome MIM#606170 to SBBYSS syndrome MIM#603736; Genitopatellar syndrome MIM#606170; KAT6B-related multiple congenital anomalies syndrome MONDO:0036042
Intellectual disability syndromic and non-syndromic v0.5725 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Intellectual disability syndromic and non-syndromic v0.5724 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2502 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Genetic Epilepsy v0.2501 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Genetic Epilepsy v0.2500 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.252 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Developmental and epileptic encephalopathy 113, MIM# 620772
Microcephaly v1.251 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1620 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Mendeliome v1.1619 SV2A Zornitza Stark edited their review of gene: SV2A: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SV2A-related, Developmental and epileptic encephalopathy 113, MIM# 620772
Fetal anomalies v1.220 PRDM6 Ain Roesley Classified gene: PRDM6 as Amber List (moderate evidence)
Fetal anomalies v1.220 PRDM6 Ain Roesley Gene: prdm6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.219 PRDM6 Ain Roesley edited their review of gene: PRDM6: Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.219 WASHC5 Ain Roesley Classified gene: WASHC5 as Green List (high evidence)
Fetal anomalies v1.219 WASHC5 Ain Roesley Gene: washc5 has been classified as Green List (High Evidence).
Fetal anomalies v1.218 WASHC5 Ain Roesley reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 1 MIM#220210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.218 SLC37A4 Ain Roesley Classified gene: SLC37A4 as Amber List (moderate evidence)
Fetal anomalies v1.218 SLC37A4 Ain Roesley Gene: slc37a4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.217 SLC37A4 Ain Roesley reviewed gene: SLC37A4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v1.217 RBFOX2 Ain Roesley Marked gene: RBFOX2 as ready
Fetal anomalies v1.217 RBFOX2 Ain Roesley Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.217 RBFOX2 Ain Roesley Classified gene: RBFOX2 as Amber List (moderate evidence)
Fetal anomalies v1.217 RBFOX2 Ain Roesley Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.216 RBFOX2 Ain Roesley gene: RBFOX2 was added
gene: RBFOX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RBFOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX2 were set to 26785492; 27670201; 27485310; 25205790; 35137168; 26785492; 37165897
Review for gene: RBFOX2 was set to AMBER
gene: RBFOX2 was marked as current diagnostic
Added comment: PMID: 37165897
1x 'splice altering' de novo in in an individual with HLSH + AVSD

- PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Sources: Literature
Fetal anomalies v1.215 PRDM6 Ain Roesley reviewed gene: PRDM6: Rating: ; Mode of pathogenicity: None; Publications: 38071433; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Congenital Heart Defect v0.414 RBFOX2 Ain Roesley Publications for gene: RBFOX2 were set to 26785492; 27670201; 27485310; 25205790; 35137168; 26785492
Congenital Heart Defect v0.413 RBFOX2 Ain Roesley commented on gene: RBFOX2
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 KDR Ain Roesley reviewed gene: KDR: Rating: GREEN; Mode of pathogenicity: None; Publications: 34113005, 30232381, 28991257, 30232381; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v1.215 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Fetal anomalies v1.215 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Fetal anomalies v1.214 KDR Ain Roesley Marked gene: KDR as ready
Fetal anomalies v1.214 KDR Ain Roesley Gene: kdr has been classified as Red List (Low Evidence).
Fetal anomalies v1.214 KDR Ain Roesley Publications for gene: KDR were set to 34113005; 30232381
Fetal anomalies v1.213 KDR Ain Roesley Mode of inheritance for gene: KDR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.212 KDR Ain Roesley edited their review of gene: KDR: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.212 KDR Ain Roesley edited their review of gene: KDR: Changed rating: GREEN; Changed publications: 34113005, 30232381, 28991257, 30232381; Set current diagnostic: yes
Fetal anomalies v1.212 KDR Ain Roesley changed review comment from: PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense
Sources: Literature; to: GREEN for AD
RED for AR

PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID: 34328347;
cohort of ToF, looking into LoF variants
4x identified + 1x classified as VUS (stop gain in penultimate exon)
1x stop gain citing PMID: 28991257

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense



Sources: Literature
Fetal anomalies v1.212 KDR Ain Roesley gene: KDR was added
gene: KDR was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KDR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDR were set to 34113005; 30232381
Phenotypes for gene: KDR were set to Tetralogy of Fallot
Added comment: PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense
Sources: Literature
Fetal anomalies v1.211 IRX4 Ain Roesley Marked gene: IRX4 as ready
Fetal anomalies v1.211 IRX4 Ain Roesley Gene: irx4 has been classified as Red List (Low Evidence).
Fetal anomalies v1.211 IRX4 Ain Roesley gene: IRX4 was added
gene: IRX4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IRX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRX4 were set to 21544582
Phenotypes for gene: IRX4 were set to Ventricular septal defect
Review for gene: IRX4 was set to RED
gene: IRX4 was marked as current diagnostic
Added comment: Two individuals with novel missense variants identified in a large cohort in 2011.

nothing new in punned
Sources: Literature
Fetal anomalies v1.210 HEY2 Ain Roesley Marked gene: HEY2 as ready
Fetal anomalies v1.210 HEY2 Ain Roesley Gene: hey2 has been classified as Red List (Low Evidence).
Fetal anomalies v1.210 HEY2 Ain Roesley gene: HEY2 was added
gene: HEY2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HEY2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: HEY2 were set to 32820247
Phenotypes for gene: HEY2 were set to congenital heart defects and thoracic aortic aneurysms
Review for gene: HEY2 was set to RED
gene: HEY2 was marked as current diagnostic
Added comment: A very large family affected by CHD and familial thoracic aortic aneurysms. Trio genome sequencing was carried out in an index patient with critical CHD, and family members had either exome or Sanger sequencing. Identified homozygous loss-of-function variant (c.318_319delAG, p.G108*) in HEY2 in 3 individuals in family with critical CHD, whereas the 20 heterozygous carriers show a spectrum of CVDs (CHD and FTAA, but varying expressivity and incomplete penetrance).

Other studies show that knockout of HEY2 in mice results in cardiovascular defects (CVDs), including septal defects, cardiomyopathy, a thin-walled aorta, and valve anomalies.
Sources: Literature
Fetal anomalies v1.209 DOHH Ain Roesley Marked gene: DOHH as ready
Fetal anomalies v1.209 DOHH Ain Roesley Gene: dohh has been classified as Green List (High Evidence).
Fetal anomalies v1.209 DOHH Ain Roesley Classified gene: DOHH as Green List (high evidence)
Fetal anomalies v1.209 DOHH Ain Roesley Gene: dohh has been classified as Green List (High Evidence).
Fetal anomalies v1.208 DOHH Ain Roesley changed review comment from: 4 families - 5 affecteds

1x cardiomyopathy at prenatal examination
4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

microcephaly was post-natal
Sources: Literature; to: 4 families - 5 affecteds

prenatal examination:
1x cardiomyopathy
1x increased nuchal translucency; chylothorax

post-natal:
4/5 presented with CHD - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

5/5 microcephaly
Fetal anomalies v1.208 DOHH Ain Roesley gene: DOHH was added
gene: DOHH was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM# 620066
Review for gene: DOHH was set to GREEN
gene: DOHH was marked as current diagnostic
Added comment: 4 families - 5 affecteds

1x cardiomyopathy at prenatal examination
4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

microcephaly was post-natal
Sources: Literature
Fetal anomalies v1.207 AMOTL1 Ain Roesley Marked gene: AMOTL1 as ready
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.207 AMOTL1 Ain Roesley Classified gene: AMOTL1 as Green List (high evidence)
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.207 AMOTL1 Ain Roesley Classified gene: AMOTL1 as Green List (high evidence)
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.206 AMOTL1 Ain Roesley gene: AMOTL1 was added
gene: AMOTL1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 36751037
Phenotypes for gene: AMOTL1 were set to Orofacial clefting syndrome, MONDO:0015335, AMOTL1-related
Review for gene: AMOTL1 was set to GREEN
gene: AMOTL1 was marked as current diagnostic
Added comment: PMID: 36751037- 16 individuals from 12 families with orofacial clefting syndrome and het variants in AMOTL1. Many in 1 hotspot: 5 individuals from 3 families have R157C, 6 individuals from another 4 families have R157H, 1 has P160L, and another has Q161R. Out of this hostpaot- 1 with P368A, 1 with E507K, 1 with E579K. 7 are de novo. All but 2 have clefting, 7 are dysmorphic, 5 have hearing loss, 9 have CHD, 7 have tall stature, 6 have dev delay. Other features include liver disease, myopia, scoliosis and immune involvement.

Another 2 families have been previously reported (described in the panelapp review below) with variants in this hotspot 1 has 2 individuals with R157C, the other has 1 individual with P160L. All hotspot are absent from gnomad v2.
Sources: Literature
Fetal anomalies v1.205 AL117258.1 Ain Roesley Marked gene: AL117258.1 as ready
Fetal anomalies v1.205 AL117258.1 Ain Roesley Gene: al117258.1 has been classified as Green List (High Evidence).
Fetal anomalies v1.205 AL117258.1 Ain Roesley Classified gene: AL117258.1 as Green List (high evidence)
Fetal anomalies v1.205 AL117258.1 Ain Roesley Gene: al117258.1 has been classified as Green List (High Evidence).
Fetal anomalies v1.204 AL117258.1 Ain Roesley gene: AL117258.1 was added
gene: AL117258.1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy; congenital heart defects
Review for gene: AL117258.1 was set to GREEN
gene: AL117258.1 was marked as current diagnostic
Added comment: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Sources: Literature
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Marked gene: MED12 as ready
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Mode of inheritance for gene: MED12 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2499 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to Ohdo syndrome, X-linked MIM#300895; Lujan-Fryns syndrome MIM#309520; Opitz-Kaveggia syndrome MIM#305450
Genetic Epilepsy v0.2498 MED12 Zornitza Stark Publications for gene: MED12 were set to 33244166; 32174975; 30006928; 27312080; 33244166
Genetic Epilepsy v0.2497 MED12 Zornitza Stark Publications for gene: MED12 were set to
Genetic Epilepsy v0.2497 MED12 Zornitza Stark Mode of inheritance for gene: MED12 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2496 MECP2 Zornitza Stark Marked gene: MECP2 as ready
Genetic Epilepsy v0.2496 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2496 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from to Rett syndrome, MIM# 312750; Intellectual developmental disorder, X-linked, syndromic 13, MIM# 300055; Encephalopathy, neonatal severe, MIM# 300673
Genetic Epilepsy v0.2495 MECP2 Zornitza Stark Publications for gene: MECP2 were set to
Genetic Epilepsy v0.2494 MECP2 Zornitza Stark Mode of inheritance for gene: MECP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2493 MBOAT7 Zornitza Stark Marked gene: MBOAT7 as ready
Genetic Epilepsy v0.2493 MBOAT7 Zornitza Stark Gene: mboat7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2493 MBOAT7 Zornitza Stark Phenotypes for gene: MBOAT7 were changed from to intellectual disability MIM#617188
Genetic Epilepsy v0.2492 MBOAT7 Zornitza Stark Publications for gene: MBOAT7 were set to
Genetic Epilepsy v0.2491 MBOAT7 Zornitza Stark Mode of inheritance for gene: MBOAT7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from to Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820
Genetic Epilepsy v0.2489 KCNJ11 Zornitza Stark Publications for gene: KCNJ11 were set to
Genetic Epilepsy v0.2488 KCNJ11 Zornitza Stark Mode of inheritance for gene: KCNJ11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from to Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Genetic Epilepsy v0.2486 DYNC1H1 Zornitza Stark Publications for gene: DYNC1H1 were set to
Genetic Epilepsy v0.2485 DYNC1H1 Zornitza Stark Mode of inheritance for gene: DYNC1H1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2484 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Prepair 1000+ v1.6 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Amber List (moderate evidence)
Prepair 1000+ v1.6 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark changed review comment from: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.

New HGNC approved name is ADPRS.; to: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.

New HGNC approved name is ADPRS.

To be upgraded to GREEN in next version of panel.
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark edited their review of gene: ADPRHL2: Changed rating: AMBER
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Marked gene: MAP2K2 as ready
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Gene: map2k2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from to Cardiofaciocutaneous syndrome 4, MIM# 615280
Genetic Epilepsy v0.2483 MAP2K2 Zornitza Stark Publications for gene: MAP2K2 were set to
Genetic Epilepsy v0.2482 MAP2K2 Zornitza Stark Mode of pathogenicity for gene: MAP2K2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genetic Epilepsy v0.2481 MAP2K2 Zornitza Stark Mode of inheritance for gene: MAP2K2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from to Cardiofaciocutaneous syndrome 3, MIM# 615279
Genetic Epilepsy v0.2479 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to
Genetic Epilepsy v0.2478 MAP2K1 Zornitza Stark Mode of pathogenicity for gene: MAP2K1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genetic Epilepsy v0.2477 MAP2K1 Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2476 MAF Zornitza Stark Marked gene: MAF as ready
Genetic Epilepsy v0.2476 MAF Zornitza Stark Gene: maf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2476 MAF Zornitza Stark Phenotypes for gene: MAF were changed from to Ayme-Gripp syndrome (MIM#601088)
Genetic Epilepsy v0.2475 MAF Zornitza Stark Publications for gene: MAF were set to
Genetic Epilepsy v0.2474 MAF Zornitza Stark Mode of inheritance for gene: MAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from to NESCAV syndrome, MIM# 614255
Genetic Epilepsy v0.2472 KIF1A Zornitza Stark Publications for gene: KIF1A were set to
Genetic Epilepsy v0.2471 KIF1A Zornitza Stark Mode of inheritance for gene: KIF1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2470 KIF1A Zornitza Stark changed review comment from: HSN2C is an autosomal recessive disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs. At least 4 families reported, although 3 shared same founder variant.

De novo variants in this gene are also more commonly associated with spastic paraplegia, and a complex neurodevelopmental disorder, NESCAV syndrome.; to: De novo variants in this gene are also more commonly associated with spastic paraplegia, and a complex neurodevelopmental disorder, NESCAV syndrome, which can include seizures.
Genetic Epilepsy v0.2470 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: NESCAV syndrome, MIM# 614255; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from to lkuraya-Kucinskas syndrome, MIM# 617822
Genetic Epilepsy v0.2469 KIAA1109 Zornitza Stark Publications for gene: KIAA1109 were set to
Genetic Epilepsy v0.2468 KIAA1109 Zornitza Stark Mode of inheritance for gene: KIAA1109 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Marked gene: KCTD7 as ready
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Gene: kctd7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Phenotypes for gene: KCTD7 were changed from to Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726), AR
Genetic Epilepsy v0.2466 KCTD7 Zornitza Stark Publications for gene: KCTD7 were set to
Genetic Epilepsy v0.2465 KCTD7 Zornitza Stark Mode of inheritance for gene: KCTD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Marked gene: ITPA as ready
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Gene: itpa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Phenotypes for gene: ITPA were changed from to Developmental and epileptic encephalopathy 35, MIM# 616647
Genetic Epilepsy v0.2463 ITPA Zornitza Stark Publications for gene: ITPA were set to
Genetic Epilepsy v0.2462 ITPA Zornitza Stark Mode of inheritance for gene: ITPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Gene: ikbkg has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Phenotypes for gene: IKBKG were changed from to Incontinentia pigmenti, MIM# 308300
Genetic Epilepsy v0.2460 IKBKG Zornitza Stark Publications for gene: IKBKG were set to
Genetic Epilepsy v0.2459 IKBKG Zornitza Stark Mode of inheritance for gene: IKBKG was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2458 IKBKG Zornitza Stark changed review comment from: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.; to: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.

Seizures reported in the IP phenotype.
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Marked gene: IFIH1 as ready
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Gene: ifih1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Phenotypes for gene: IFIH1 were changed from to Aicardi-Goutieres syndrome 7, MIM#615846
Genetic Epilepsy v0.2457 IFIH1 Zornitza Stark Publications for gene: IFIH1 were set to
Genetic Epilepsy v0.2456 IFIH1 Zornitza Stark Mode of pathogenicity for gene: IFIH1 was changed from to Other
Genetic Epilepsy v0.2455 IFIH1 Zornitza Stark Mode of inheritance for gene: IFIH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Marked gene: IDH2 as ready
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Gene: idh2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Phenotypes for gene: IDH2 were changed from to D-2-hydroxyglutaric aciduria 2, MIM# 613657
Genetic Epilepsy v0.2453 IDH2 Zornitza Stark Publications for gene: IDH2 were set to
Genetic Epilepsy v0.2452 IDH2 Zornitza Stark Mode of inheritance for gene: IDH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Marked gene: HTRA2 as ready
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Gene: htra2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Phenotypes for gene: HTRA2 were changed from to 3-methylglutaconic aciduria, type VIII, MIM# 617248
Genetic Epilepsy v0.2450 HTRA2 Zornitza Stark Publications for gene: HTRA2 were set to
Genetic Epilepsy v0.2449 HTRA2 Zornitza Stark Mode of inheritance for gene: HTRA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark changed review comment from: Multiple families reported with bi-allelic variants in HSPD1 and hypomyelinating leukodystrophy. Supportive mouse model. In addition, two unrelated individuals reported with same de novo missense p.Leu47Val and leukodystrophy.

In addition, mono-allelic variants found in families with SPG.; to: Multiple families reported with bi-allelic variants in HSPD1 and hypomyelinating leukodystrophy. Supportive mouse model. In addition, two unrelated individuals reported with same de novo missense p.Leu47Val and leukodystrophy.

In addition, mono-allelic variants found in families with SPG, not relevant to this panel.
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark edited their review of gene: HSPD1: Changed phenotypes: Leukodystrophy, hypomyelinating, 4, MIM# 612233; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Marked gene: HSPD1 as ready
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Phenotypes for gene: HSPD1 were changed from to Leukodystrophy, hypomyelinating, 4, MIM# 612233
Genetic Epilepsy v0.2447 HSPD1 Zornitza Stark Mode of inheritance for gene: HSPD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2446 HSPD1 Zornitza Stark Publications for gene: HSPD1 were set to
Genetic Epilepsy v0.2445 HSPD1 Zornitza Stark Mode of inheritance for gene: HSPD1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
Genetic Epilepsy v0.2443 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Genetic Epilepsy v0.2442 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Marked gene: HRAS as ready
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from Costello syndrome, MIM# 218040 to Costello syndrome, MIM# 218040
Genetic Epilepsy v0.2440 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from to Costello syndrome, MIM# 218040
Genetic Epilepsy v0.2439 HRAS Zornitza Stark Publications for gene: HRAS were set to
Genetic Epilepsy v0.2438 HRAS Zornitza Stark Mode of pathogenicity for gene: HRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genetic Epilepsy v0.2437 HRAS Zornitza Stark Mode of inheritance for gene: HRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Marked gene: HMGCL as ready
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Gene: hmgcl has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Phenotypes for gene: HMGCL were changed from to HMG-CoA lyase deficiency, MIM# 246450
Genetic Epilepsy v0.2435 HMGCL Zornitza Stark Publications for gene: HMGCL were set to
Genetic Epilepsy v0.2434 HMGCL Zornitza Stark Mode of inheritance for gene: HMGCL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Marked gene: HLCS as ready
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Gene: hlcs has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Phenotypes for gene: HLCS were changed from to Holocarboxylase synthetase deficiency, MIM# 253270
Genetic Epilepsy v0.2432 HLCS Zornitza Stark Publications for gene: HLCS were set to
Genetic Epilepsy v0.2431 HLCS Zornitza Stark Mode of inheritance for gene: HLCS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Marked gene: HEXB as ready
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Gene: hexb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Phenotypes for gene: HEXB were changed from to Sandhoff disease, infantile, juvenile, and adult forms, MIM# 268800; MONDO:0010006
Genetic Epilepsy v0.2429 HEXB Zornitza Stark Mode of inheritance for gene: HEXB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Marked gene: HEXA as ready
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Phenotypes for gene: HEXA were changed from to GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800
Genetic Epilepsy v0.2427 HEXA Zornitza Stark Publications for gene: HEXA were set to
Genetic Epilepsy v0.2426 HEXA Zornitza Stark Mode of inheritance for gene: HEXA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Marked gene: HEPACAM as ready
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Gene: hepacam has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926
Genetic Epilepsy v0.2424 HEPACAM Zornitza Stark Publications for gene: HEPACAM were set to
Genetic Epilepsy v0.2423 HEPACAM Zornitza Stark Mode of inheritance for gene: HEPACAM was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Marked gene: HAX1 as ready
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Gene: hax1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Phenotypes for gene: HAX1 were changed from to Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738; Kostmann syndrome MONDO:0012548
Genetic Epilepsy v0.2421 HAX1 Zornitza Stark Publications for gene: HAX1 were set to
Genetic Epilepsy v0.2420 HAX1 Zornitza Stark Mode of inheritance for gene: HAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Marked gene: GOSR2 as ready
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Phenotypes for gene: GOSR2 were changed from to Epilepsy, progressive myoclonic 6 , MIM#614018
Genetic Epilepsy v0.2418 GOSR2 Zornitza Stark Publications for gene: GOSR2 were set to
Genetic Epilepsy v0.2417 GOSR2 Zornitza Stark Mode of inheritance for gene: GOSR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Gene: gnaq has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Phenotypes for gene: GNAQ were changed from to Sturge-Weber syndrome, somatic, mosaic 185300
Genetic Epilepsy v0.2415 GNAQ Zornitza Stark Publications for gene: GNAQ were set to
Genetic Epilepsy v0.2414 GNAQ Zornitza Stark Mode of pathogenicity for gene: GNAQ was changed from to Other
Genetic Epilepsy v0.2413 GNAQ Zornitza Stark Mode of inheritance for gene: GNAQ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2412 GNAQ Zornitza Stark Tag somatic tag was added to gene: GNAQ.
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Marked gene: GM2A as ready
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Gene: gm2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Phenotypes for gene: GM2A were changed from to GM2-gangliosidosis, AB variant MIM#272750
Genetic Epilepsy v0.2411 GM2A Zornitza Stark Publications for gene: GM2A were set to
Genetic Epilepsy v0.2410 GM2A Zornitza Stark Mode of inheritance for gene: GM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Marked gene: GLUL as ready
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from to Glutamine deficiency, congenital MIM#610015
Genetic Epilepsy v0.2408 GLUL Zornitza Stark Publications for gene: GLUL were set to
Genetic Epilepsy v0.2407 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2406 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutamine deficiency, congenital MIM#610015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Marked gene: GLUD1 as ready
Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Phenotypes for gene: GLUD1 were changed from to Hyperinsulinism-hyperammonemia syndrome, MIM# 606762
Genetic Epilepsy v0.2405 GLUD1 Zornitza Stark Publications for gene: GLUD1 were set to
Genetic Epilepsy v0.2404 GLUD1 Zornitza Stark Mode of inheritance for gene: GLUD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2403 GLUD1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Hypoglycaemic seizures.
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Marked gene: GLDC as ready
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Phenotypes for gene: GLDC were changed from to Glycine encephalopathy (MIM#605899)
Genetic Epilepsy v0.2402 GLDC Zornitza Stark Publications for gene: GLDC were set to
Genetic Epilepsy v0.2401 GLDC Zornitza Stark Mode of inheritance for gene: GLDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from to GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600
Genetic Epilepsy v0.2399 GLB1 Zornitza Stark Publications for gene: GLB1 were set to
Genetic Epilepsy v0.2398 GLB1 Zornitza Stark Mode of inheritance for gene: GLB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Marked gene: GFM1 as ready
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Phenotypes for gene: GFM1 were changed from to Combined oxidative phosphorylation deficiency 1 MIM#609060
Genetic Epilepsy v0.2396 GFM1 Zornitza Stark Publications for gene: GFM1 were set to
Genetic Epilepsy v0.2395 GFM1 Zornitza Stark Mode of inheritance for gene: GFM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Marked gene: GFAP as ready
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Gene: gfap has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Phenotypes for gene: GFAP were changed from to Alexander disease, MIM# 203450
Genetic Epilepsy v0.2393 GFAP Zornitza Stark Publications for gene: GFAP were set to
Genetic Epilepsy v0.2392 GFAP Zornitza Stark Mode of inheritance for gene: GFAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910
Genetic Epilepsy v0.2390 GCH1 Zornitza Stark Publications for gene: GCH1 were set to
Genetic Epilepsy v0.2389 GCH1 Zornitza Stark Mode of inheritance for gene: GCH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2388 GCH1 Zornitza Stark Deleted their comment
Genetic Epilepsy v0.2388 GCH1 Zornitza Stark edited their review of gene: GCH1: Added comment: Well established gene-disease association, seizures are part of the phenotype.; Changed publications: 7730309; Changed phenotypes: Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2388 GALC Zornitza Stark Marked gene: GALC as ready
Genetic Epilepsy v0.2388 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2388 GALC Zornitza Stark Phenotypes for gene: GALC were changed from to Krabbe disease, MIM# 245200; MONDO:0009499
Genetic Epilepsy v0.2387 GALC Zornitza Stark Publications for gene: GALC were set to
Genetic Epilepsy v0.2386 GALC Zornitza Stark Mode of inheritance for gene: GALC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2385 GALC Zornitza Stark changed review comment from: Krabbe disease is an autosomal recessive lysosomal disorder affecting the white matter of the central and peripheral nervous systems. Most patients present within the first 6 months of life with 'infantile' or 'classic' disease manifest as extreme irritability, spasticity, and developmental delay. There is severe motor and mental deterioration, leading to decerebration and death by age 2 years. Approximately 10 to 15% of patients have a later onset, commonly differentiated as late-infantile (6 months to 3 years), juvenile (3 to 8 years), and even adult-onset forms. Multiple families reported.; to: Krabbe disease is an autosomal recessive lysosomal disorder affecting the white matter of the central and peripheral nervous systems. Most patients present within the first 6 months of life with 'infantile' or 'classic' disease manifest as extreme irritability, spasticity, and developmental delay. There is severe motor and mental deterioration, leading to decerebration and death by age 2 years. Approximately 10 to 15% of patients have a later onset, commonly differentiated as late-infantile (6 months to 3 years), juvenile (3 to 8 years), and even adult-onset forms. Multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Marked gene: FUCA1 as ready
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Gene: fuca1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Phenotypes for gene: FUCA1 were changed from to Fucosidosis, MIM# 230000; MONDO:0009254
Genetic Epilepsy v0.2384 FUCA1 Zornitza Stark Publications for gene: FUCA1 were set to
Genetic Epilepsy v0.2383 FUCA1 Zornitza Stark Mode of inheritance for gene: FUCA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2382 FUCA1 Zornitza Stark changed review comment from: Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Well established gene-disease association, multiple families reported.; to: Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Well established gene-disease association, multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Phenotypes for gene: FRRS1L were changed from to Developmental and epileptic encephalopathy, 37 MONDO:0014859
Genetic Epilepsy v0.2381 FRRS1L Zornitza Stark Publications for gene: FRRS1L were set to
Genetic Epilepsy v0.2380 FRRS1L Zornitza Stark Mode of inheritance for gene: FRRS1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Publications for gene: DPM1 were set to 23856421
Genetic Epilepsy v0.2378 DPM1 Zornitza Stark Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, 608799
Genetic Epilepsy v0.2377 DPM1 Zornitza Stark Publications for gene: DPM1 were set to
Genetic Epilepsy v0.2376 DPM1 Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2375 DPM1 Zornitza Stark reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ie, 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Marked gene: DNM1L as ready
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Gene: dnm1l has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR) to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR)
Genetic Epilepsy v0.2374 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR)
Genetic Epilepsy v0.2374 DNM1L Zornitza Stark Mode of inheritance for gene: DNM1L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2373 DNM1L Zornitza Stark Mode of inheritance for gene: DNM1L was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Tag new gene name tag was added to gene: ADPRHL2.
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Green List (high evidence)
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.4 ADPRHL2 Zornitza Stark reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1619 GNE Zornitza Stark Phenotypes for gene: GNE were changed from Nonaka myopathy 605820; Sialuria MIM#269921; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways) to Thrombocytopenia 12 with or without myopathy, MIM#620757; Nonaka myopathy 605820; Sialuria MIM#269921; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Mendeliome v1.1618 GNE Zornitza Stark edited their review of gene: GNE: Changed phenotypes: Thrombocytopenia 12 with or without myopathy, MIM#620757, Nonaka myopathy 605820, Sialuria MIM#269921, ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Bleeding and Platelet Disorders v1.29 GNE Zornitza Stark Phenotypes for gene: GNE were changed from Thrombocytopaenia; Myopathy to Thrombocytopenia 12 with or without myopathy, MIM#620757
Bleeding and Platelet Disorders v1.28 GNE Zornitza Stark edited their review of gene: GNE: Changed phenotypes: Thrombocytopenia 12 with or without myopathy, MIM#620757
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Marked gene: ANK2 as ready
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Gene: ank2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Added comment: Comment on phenotypes: Association is disputed, gene associated to a neurodevelopmental disorder
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Phenotypes for gene: ANK2 were changed from to Cardiac arrhythmia, ankyrin-B-related MIM#600919; Long QT syndrome 4 MIM#600919
Cardiomyopathy_Paediatric v0.183 ANK2 Elena Savva Classified gene: ANK2 as Red List (low evidence)
Cardiomyopathy_Paediatric v0.183 ANK2 Elena Savva Gene: ank2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Marked gene: FOXG1 as ready
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Phenotypes for gene: FOXG1 were changed from to Rett syndrome, congenital variant, MIM# 613454
Genetic Epilepsy v0.2371 FOXG1 Zornitza Stark Publications for gene: FOXG1 were set to
Genetic Epilepsy v0.2370 FOXG1 Zornitza Stark Mode of inheritance for gene: FOXG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2369 FOXG1 Zornitza Stark reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rett syndrome, congenital variant, MIM# 613454; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, MIM# 614678
Genetic Epilepsy v0.2368 EXOSC3 Zornitza Stark Publications for gene: EXOSC3 were set to
Genetic Epilepsy v0.2367 EXOSC3 Zornitza Stark Mode of inheritance for gene: EXOSC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2366 EXOSC3 Zornitza Stark changed review comment from: Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement. PCH1B can be divided into mild, moderate, and severe subgroups that vary in age at onset, progression, clinical and neuroradiologic severity, and survival. Multiple families reported.; to: Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement. PCH1B can be divided into mild, moderate, and severe subgroups that vary in age at onset, progression, clinical and neuroradiologic severity, and survival. Multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Marked gene: EPM2A as ready
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Gene: epm2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from Lafora disease MONDO:0009697 to Lafora disease MONDO:0009697
Genetic Epilepsy v0.2365 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from to Lafora disease MONDO:0009697
Genetic Epilepsy v0.2364 EPM2A Zornitza Stark Publications for gene: EPM2A were set to
Genetic Epilepsy v0.2363 EPM2A Zornitza Stark Mode of inheritance for gene: EPM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1618 SAMD7 Zornitza Stark Phenotypes for gene: SAMD7 were changed from Macular dystrophy, retinal, SAMD7-related MONDO:0031166 to Macular dystrophy with or without cone dysfunction, MIM# 620762
Mendeliome v1.1617 SAMD7 Zornitza Stark reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Macular dystrophy with or without cone dysfunction, MIM# 620762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.45 SAMD7 Zornitza Stark Phenotypes for gene: SAMD7 were changed from Macular dystrophy, retinal, SAMD7-related MONDO:0031166 to Macular dystrophy with or without cone dysfunction, MIM# 620762
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Macular dystrophy with or without cone dysfunction, MIM# 620762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1617 FHL2 Zornitza Stark Marked gene: FHL2 as ready
Mendeliome v1.1617 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1617 FHL2 Zornitza Stark Classified gene: FHL2 as Amber List (moderate evidence)
Mendeliome v1.1617 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1616 FHL2 Zornitza Stark gene: FHL2 was added
gene: FHL2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FHL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FHL2 were set to 36854411; 25358972
Phenotypes for gene: FHL2 were set to Cardiomyopathy, MONDO:0004994, FHL2-related
Review for gene: FHL2 was set to AMBER
Added comment: Emerging evidence that variants in this gene may be associated with cardiomyopathy.

Reports of HCM and DCM.

c.391C>T (p.Arg131Cys) may be recurrent in early-onset DCM.
Sources: Expert Review
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Marked gene: FHL2 as ready
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Classified gene: FHL2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.181 FHL2 Zornitza Stark gene: FHL2 was added
gene: FHL2 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: FHL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FHL2 were set to 36854411; 25358972
Phenotypes for gene: FHL2 were set to Cardiomyopathy, MONDO:0004994, FHL2-related
Review for gene: FHL2 was set to AMBER
Added comment: Emerging evidence that variants in this gene may be associated with cardiomyopathy.

Reports of HCM and DCM.

c.391C>T (p.Arg131Cys) may be recurrent in early-onset DCM.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5724 ZFHX3 Zornitza Stark Publications for gene: ZFHX3 were set to 37292950
Intellectual disability syndromic and non-syndromic v0.5723 ZFHX3 Zornitza Stark edited their review of gene: ZFHX3: Added comment: Now published PMID 38412861; Changed publications: 38412861
Mendeliome v1.1615 ZFHX3 Zornitza Stark Publications for gene: ZFHX3 were set to
Mendeliome v1.1614 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Mendeliome v1.1614 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Mendeliome v1.1614 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Mendeliome v1.1614 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Mendeliome v1.1613 ZRSR2 Zornitza Stark gene: ZRSR2 was added
gene: ZRSR2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5723 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Genetic Epilepsy v0.2362 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Genetic epilepsy with febrile seizures plus; Developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Genetic Epilepsy v0.2361 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Mendeliome v1.1612 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Genetic epilepsy with febrile seizures plus; Developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Mendeliome v1.1611 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Intellectual disability syndromic and non-syndromic v0.5722 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from Parkinsonism; Intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Intellectual disability syndromic and non-syndromic v0.5721 PTRHD1 Zornitza Stark edited their review of gene: PTRHD1: Changed phenotypes: Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Mendeliome v1.1611 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from Parkinsonism; Intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Early-onset Parkinson disease v0.295 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from early-onset parkinsonism; intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Early-onset Parkinson disease v0.294 PTRHD1 Zornitza Stark reviewed gene: PTRHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 DMP1 Zornitza Stark Marked gene: DMP1 as ready
Osteopetrosis v0.34 DMP1 Zornitza Stark Gene: dmp1 has been classified as Green List (High Evidence).
Osteopetrosis v0.34 DMP1 Zornitza Stark Classified gene: DMP1 as Green List (high evidence)
Osteopetrosis v0.34 DMP1 Zornitza Stark Gene: dmp1 has been classified as Green List (High Evidence).
Osteopetrosis v0.33 DMP1 Zornitza Stark gene: DMP1 was added
gene: DMP1 was added to Osteopetrosis. Sources: Expert Review
Mode of inheritance for gene: DMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMP1 were set to 17033625
Phenotypes for gene: DMP1 were set to Hypophosphataemic rickets, MIM#600980
Review for gene: DMP1 was set to GREEN
Added comment: Included due to phenotypic overlap: osteosclerotic changes on X-rays, severe in some individuals.
Sources: Expert Review
Mendeliome v1.1610 BBS4 Bryony Thompson reviewed gene: BBS4: Rating: RED; Mode of pathogenicity: None; Publications: 37588201; Phenotypes: autosomal dominant polycystic liver disease MONDO:0000447; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1610 BBS4 Bryony Thompson Deleted their review
Mendeliome v1.1610 ZFHX3 Lucy Spencer reviewed gene: ZFHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38412861; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), ZFHX3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1610 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder to Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v1.1609 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder to Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v1.1608 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Changed phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, EFEMP1-related connective tissue disorder, Glaucoma 1, open angle, H, MIM# 611276
Glaucoma congenital v1.9 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Juvenile-onset open angle glaucoma, MONDO:0020367, EFEMP1-related to Glaucoma 1, open angle, H, MIM# 611276
Glaucoma congenital v1.8 EFEMP1 Zornitza Stark reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glaucoma 1, open angle, H, MIM# 611276; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Phenotypes for gene: DIAPH1 were changed from to Seizures, cortical blindness, microcephaly syndrome, MIM# 616632
Genetic Epilepsy v0.2360 DIAPH1 Zornitza Stark Publications for gene: DIAPH1 were set to
Genetic Epilepsy v0.2359 DIAPH1 Zornitza Stark Mode of inheritance for gene: DIAPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2358 DIAPH1 Zornitza Stark reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Seizures, cortical blindness, microcephaly syndrome, MIM# 616632; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Phenotypes for gene: DHCR24 were changed from to Desmosterolosis, MIM# 602398
Genetic Epilepsy v0.2357 DHCR24 Zornitza Stark Publications for gene: DHCR24 were set to
Genetic Epilepsy v0.2356 DHCR24 Zornitza Stark Mode of inheritance for gene: DHCR24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2355 DHCR24 Zornitza Stark changed review comment from: Clinical features include multiple congenital anomalies, including contractures and brain anomalies; intellectual disability; and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.

At least 10 unrelated families reported, mouse model.; to: Clinical features include multiple congenital anomalies, including contractures and brain anomalies; intellectual disability; and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.

At least 10 unrelated families reported, mouse model. Seizures are a feature.
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Marked gene: DDX3X as ready
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Phenotypes for gene: DDX3X were changed from to Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type MIM# 300958
Genetic Epilepsy v0.2354 DDX3X Zornitza Stark Publications for gene: DDX3X were set to
Genetic Epilepsy v0.2353 DDX3X Zornitza Stark Mode of inheritance for gene: DDX3X was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2352 DDX3X Zornitza Stark changed review comment from: Syndromic X-linked mental retardation of the Snijders Blok type (MRXSSB), which occurs predominantly in females, is characterised by mildly to severely impaired intellectual development with variable other features including brain abnormalities, microcephaly, hypotonia, movement disorder and/or spasticity, ventricular enlargement, hypoplasia, and behavioural problems. Affected girls have de novo heterozygous mutations consistent with X-linked dominant inheritance. No consistent dysmorphic facial phenotype and onset in infancy.

Multiple unrelated families reported.; to: Syndromic X-linked mental retardation of the Snijders Blok type (MRXSSB), which occurs predominantly in females, is characterised by mildly to severely impaired intellectual development with variable other features including brain abnormalities, microcephaly, hypotonia, movement disorder and/or spasticity, ventricular enlargement, hypoplasia, and behavioural problems. Affected girls have de novo heterozygous mutations consistent with X-linked dominant inheritance. No consistent dysmorphic facial phenotype and onset in infancy.

Multiple unrelated families reported. Seizures are a feature.
Genetic Epilepsy v0.2352 DCX Zornitza Stark Marked gene: DCX as ready
Genetic Epilepsy v0.2352 DCX Zornitza Stark Gene: dcx has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2352 DCX Zornitza Stark Phenotypes for gene: DCX were changed from to Lissencephaly, X-linked, MIM# 300067; Subcortical laminal heterotopia, X-linked 300067
Genetic Epilepsy v0.2351 DCX Zornitza Stark Publications for gene: DCX were set to
Genetic Epilepsy v0.2350 DCX Zornitza Stark Mode of inheritance for gene: DCX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2349 DCX Zornitza Stark changed review comment from: DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome. Multiple affected families reported.; to: DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome. Multiple affected families reported. Seizures are a feature of the condition.
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria MIM#600721
Genetic Epilepsy v0.2348 D2HGDH Zornitza Stark Publications for gene: D2HGDH were set to
Genetic Epilepsy v0.2347 D2HGDH Zornitza Stark Mode of inheritance for gene: D2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2346 D2HGDH Zornitza Stark changed review comment from: More than 3 families reported.; to: More than 3 families reported, early onset encephalopathy is a key feature.
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Marked gene: CTSD as ready
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Phenotypes for gene: CTSD were changed from to Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; MONDO:0012414
Genetic Epilepsy v0.2345 CTSD Zornitza Stark Publications for gene: CTSD were set to
Genetic Epilepsy v0.2344 CTSD Zornitza Stark Mode of inheritance for gene: CTSD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2343 CTSD Zornitza Stark changed review comment from: Neurodegenerative disorder though severe congenital forms also reported.; to: Neurodegenerative disorder though severe congenital forms also reported, seizures are a key feature.
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Marked gene: COQ9 as ready
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Gene: coq9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5, MIM#614654
Genetic Epilepsy v0.2342 COQ9 Zornitza Stark Publications for gene: COQ9 were set to
Genetic Epilepsy v0.2341 COQ9 Zornitza Stark Mode of inheritance for gene: COQ9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2340 COQ9 Zornitza Stark reviewed gene: COQ9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 5, MIM#614654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from to Coenzyme Q10 deficiency, primary, 7, MIM# 616276
Genetic Epilepsy v0.2339 COQ4 Zornitza Stark Publications for gene: COQ4 were set to
Genetic Epilepsy v0.2338 COQ4 Zornitza Stark Mode of inheritance for gene: COQ4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Marked gene: COQ2 as ready
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from to Coenzyme Q10 deficiency, primary, 1, MIM# 607426; MONDO:0011829
Genetic Epilepsy v0.2336 COQ2 Zornitza Stark Publications for gene: COQ2 were set to
Genetic Epilepsy v0.2335 COQ2 Zornitza Stark Mode of inheritance for gene: COQ2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.203 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Feingold syndrome 1 (MIM#164280); Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Feingold syndrome 1 (MIM#164280); Megalencephaly-polydactyly syndrome, MIM# 620748
Fetal anomalies v1.202 MYCN Zornitza Stark edited their review of gene: MYCN: Changed phenotypes: Feingold syndrome 1, MIM# 164280, Megalencephaly-polydactyly syndrome, MIM# 620748
Hand and foot malformations v0.73 MYCN Zornitza Stark Marked gene: MYCN as ready
Hand and foot malformations v0.73 MYCN Zornitza Stark Gene: mycn has been classified as Green List (High Evidence).
Hand and foot malformations v0.73 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280 to Megalencephaly-polydactyly syndrome, MIM# 620748; Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280
Hand and foot malformations v0.72 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.276 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Megalencephaly-polydactyly syndrome, MIM# 620748
Polydactyly v0.275 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.140 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Megalencephaly-polydactyly syndrome, MIM# 620748
Macrocephaly_Megalencephaly v0.139 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5721 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Intellectual disability syndromic and non-syndromic v0.5720 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.519 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Callosome v0.518 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.21 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Muscular dystrophy and myopathy_Paediatric v1.20 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.251 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Microcephaly v1.250 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1608 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Mendeliome v1.1607 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autism v0.197 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Autism v0.196 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1607 RREB1 Zornitza Stark Phenotypes for gene: RREB1 were changed from Noonan syndrome-like disorder to Rasopathy, MONDO:0021060, RREB1-related
Microcephaly v1.250 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Mendeliome v1.1606 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Cataract v0.364 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Neurodevelopmental disorder, MONDO:0700092, RGS6-related to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Cataract v0.363 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.20 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152, SNUPN-related
Mendeliome v1.1604 CORIN Zornitza Stark Phenotypes for gene: CORIN were changed from Preeclampsia/eclampsia 5 MIM#614595; ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734) to Preeclampsia/eclampsia 5 MIM#614595; Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Mendeliome v1.1603 CORIN Zornitza Stark Publications for gene: CORIN were set to 22437503
Mendeliome v1.1602 CORIN Zornitza Stark Phenotypes for gene: CORIN were changed from Preeclampsia/eclampsia 5 MIM#614595 to Preeclampsia/eclampsia 5 MIM#614595; ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Genetic Epilepsy v0.2334 DIP2C Zornitza Stark Classified gene: DIP2C as Green List (high evidence)
Genetic Epilepsy v0.2334 DIP2C Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2333 DIP2C Zornitza Stark reviewed gene: DIP2C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DIP2C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.202 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Fetal anomalies v1.202 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Fetal anomalies v1.202 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Fetal anomalies v1.202 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Fetal anomalies v1.201 CELSR3 Zornitza Stark edited their review of gene: CELSR3: Changed rating: GREEN
Fetal anomalies v1.201 CELSR3 Zornitza Stark gene: CELSR3 was added
gene: CELSR3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.137 CELSR3 Zornitza Stark gene: CELSR3 was added
gene: CELSR3 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.136 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.136 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.136 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to CHARGE syndrome MIM#214800
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.135 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CHARGE syndrome MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 ACE Zornitza Stark Marked gene: ACE as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 ACE Zornitza Stark Gene: ace has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 ACE Zornitza Stark Deleted their review
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Mendeliome v1.1601 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Mendeliome v1.1601 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Mendeliome v1.1601 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Mendeliome v1.1601 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Regression v0.547 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Regression v0.547 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.547 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Regression v0.547 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.546 CIAO1 Zornitza Stark gene: CIAO1 was added
gene: CIAO1 was added to Regression. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Review for gene: CIAO1 was set to GREEN
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Mendeliome v1.1600 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Mendeliome v1.1600 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Mendeliome v1.1600 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Mendeliome v1.1599 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Mendeliome v1.1599 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.19 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Muscular dystrophy and myopathy_Paediatric v1.18 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neurodegenerative disease, MONDO:0005559, CIAO1-related to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Muscular dystrophy and myopathy_Paediatric v1.16 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.16 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.545 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Regression v0.545 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Regression v0.545 MMS19 Zornitza Stark gene: MMS19 was added
gene: MMS19 was added to Regression. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neurodegenerative disease, MONDO:0005559, MMS19-related
Review for gene: MMS19 was set to RED
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Genetic Epilepsy v0.2332 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Genetic Epilepsy v0.2332 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Mendeliome v1.1598 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Mendeliome v1.1598 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Mendeliome v1.1598 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Mendeliome v1.1597 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Mendeliome v1.1597 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.15 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v1.15 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Gene: mms19 has been removed from the panel.
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Hereditary Neuropathy - complex v1.10 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Intellectual disability syndromic and non-syndromic v0.5718 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Genetic Epilepsy v0.2331 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Microcephaly v1.249 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Microcephaly v1.249 NARS Zornitza Stark edited their review of gene: NARS: Changed rating: GREEN
Mendeliome v1.1596 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Fetal anomalies v1.200 NARS Zornitza Stark edited their review of gene: NARS: Changed rating: GREEN
Fetal anomalies v1.200 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Muscular dystrophy and myopathy_Paediatric v1.13 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Genetic Epilepsy v0.2331 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.13 CIAO1 Paul De Fazio gene: CIAO1 was added
gene: CIAO1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Penetrance for gene: CIAO1 were set to unknown
Review for gene: CIAO1 was set to GREEN
gene: CIAO1 was marked as current diagnostic
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Mendeliome v1.1596 CIAO1 Paul De Fazio changed review comment from: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature; to: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Mendeliome v1.1596 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Penetrance for gene: MMS19 were set to unknown
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model also showed a detrimental effect of Mms19 deficincy.
Sources: Literature
Mendeliome v1.1596 CIAO1 Paul De Fazio gene: CIAO1 was added
gene: CIAO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Penetrance for gene: CIAO1 were set to unknown
Review for gene: CIAO1 was set to GREEN
gene: CIAO1 was marked as current diagnostic
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Marked gene: SLC12A9 as ready
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 CELSR3 Crystle Lee gene: CELSR3 was added
gene: CELSR3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to PMID: 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals
Sources: Literature
Genetic Epilepsy v0.2331 DIP2C Elena Savva Marked gene: DIP2C as ready
Genetic Epilepsy v0.2331 DIP2C Elena Savva Gene: dip2c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2331 DIP2C Elena Savva Classified gene: DIP2C as Amber List (moderate evidence)
Genetic Epilepsy v0.2331 DIP2C Elena Savva Gene: dip2c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1596 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from {Lumbar disc herniation, susceptibility to} 603932 to {Lumbar disc herniation, susceptibility to} 603932; connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1595 THBS2 Ain Roesley Publications for gene: THBS2 were set to
Mendeliome v1.1594 THBS2 Ain Roesley Mode of inheritance for gene: THBS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1594 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Mendeliome v1.1594 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1593 THBS2 Chris Ciotta reviewed gene: THBS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38433265; Phenotypes: connective tissue disorder MONDO:0003900, THBS2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Genetic Epilepsy v0.2330 DIP2C Melanie Marty reviewed gene: DIP2C: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38421105; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DIP2C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Genetic Epilepsy v0.2330 DIP2C Melanie Marty Deleted their review
Genetic Epilepsy v0.2330 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Mendeliome v1.1593 UBAP1L Seb Lunke Marked gene: UBAP1L as ready
Mendeliome v1.1593 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from connective tissue disorder MONDO:0003900, THBS2-related to connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1593 UBAP1L Seb Lunke Classified gene: UBAP1L as Green List (high evidence)
Mendeliome v1.1593 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Mendeliome v1.1592 UBAP1L Seb Lunke Classified gene: UBAP1L as Green List (high evidence)
Mendeliome v1.1592 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Marked gene: THBS2 as ready
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from connective tissue disorder MONDO:0003900, THBS2-related to connective tissue disorder MONDO:0003900, THBS2-related
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from Ehlers-Danlos syndrome to connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1591 DIP2C Elena Savva Marked gene: DIP2C as ready
Mendeliome v1.1591 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Chris Ciotta edited their review of gene: THBS2: Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.; Changed phenotypes: connective tissue disorder MONDO:0003900, THBS2-related
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Marked gene: DIP2C as ready
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5717 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1591 APOLD1 Seb Lunke Marked gene: APOLD1 as ready
Mendeliome v1.1591 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Classified gene: DIP2C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1591 TOGARAM2 Zornitza Stark Marked gene: TOGARAM2 as ready
Mendeliome v1.1591 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta commented on gene: THBS2: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1591 APOLD1 Seb Lunke Classified gene: APOLD1 as Amber List (moderate evidence)
Mendeliome v1.1591 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta commented on gene: THBS2: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Mendeliome v1.1590 DIP2C Elena Savva Classified gene: DIP2C as Green List (high evidence)
Mendeliome v1.1590 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Mendeliome v1.1590 TOGARAM2 Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence)
Mendeliome v1.1590 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Mendeliome v1.1589 UBAP1L Ee Ming Wong changed review comment from: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature; to: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5716 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta edited their review of gene: THBS2: Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.; Changed phenotypes: connective tissue disorder MONDO:0003900
Mendeliome v1.1589 CORIN Daniel Flanagan reviewed gene: CORIN: Rating: RED; Mode of pathogenicity: None; Publications: 37913506, 15637153; Phenotypes: ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Marked gene: SNUPN as ready
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1589 SNUPN Seb Lunke Marked gene: SNUPN as ready
Mendeliome v1.1589 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Marked gene: SNUPN as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Marked gene: APOLD1 as ready
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v1.2 CORIN Seb Lunke Marked gene: CORIN as ready
Atrial Fibrillation v1.2 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1589 TOGARAM2 Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence)
Mendeliome v1.1589 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to Syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Atrial Fibrillation v1.2 CORIN Seb Lunke Classified gene: CORIN as Red List (low evidence)
Atrial Fibrillation v1.2 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1588 UBAP1L Ee Ming Wong gene: UBAP1L was added
gene: UBAP1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBAP1L were set to PMID: 38293907; 38420906
Phenotypes for gene: UBAP1L were set to Cone-rod dystrophy (MONDO:0015993), UBAP1L-related
Review for gene: UBAP1L was set to GREEN
gene: UBAP1L was marked as current diagnostic
Added comment: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Classified gene: APOLD1 as Amber List (moderate evidence)
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.55 TOGARAM2 Zornitza Stark Marked gene: TOGARAM2 as ready
Deafness_Isolated v1.55 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.55 TOGARAM2 Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence)
Deafness_Isolated v1.55 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Atrial Fibrillation v1.1 CORIN Daniel Flanagan gene: CORIN was added
gene: CORIN was added to Atrial Fibrillation. Sources: Expert list
Mode of inheritance for gene: CORIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CORIN were set to 37913506; 15637153
Phenotypes for gene: CORIN were set to ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Review for gene: CORIN was set to RED
Added comment: Two siblings with a homozygous loss-of-function variant in CORIN. Both presented with left atrial hypertrophic cardiomyopathy, hypertension, fibrosis, and arrhythmia isolated to the left atrium. A plasma sample obtained from one of the siblings had no detectable levels of corin.

One sibling also had a het variant, p.(Ser571Thr), in PKP2 (associated with AD ARVC). The PKP2 variant is LP/VUS in ClinVar.

Cor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Cor-/- mice also have spontaneous hypertension.
Sources: Expert list
Mendeliome v1.1588 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Mendeliome v1.1588 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1587 CELSR3 Crystle Lee gene: CELSR3 was added
gene: CELSR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to PMID: 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals

PMID: 34951123: 5 het missense variants reported in patients with febrile seizures (FS)/epilepsy. Arg3141Gln present in gnomAD (7 hets). No functional studies. Summarised as potentially associated with febrile seizures (FS)/epilepsy
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Deafness_IsolatedAndComplex v1.172 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to Syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Marked gene: UBAP1L as ready
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Gene: ubap1l has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Classified gene: UBAP1L as Green List (high evidence)
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Gene: ubap1l has been classified as Green List (High Evidence).
Mendeliome v1.1587 APOLD1 Lucy Spencer changed review comment from: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature; to: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.

SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF.
Sources: Literature
Bleeding and Platelet Disorders v1.27 APOLD1 Lucy Spencer changed review comment from: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature; to: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.

SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1587 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Cone-rod Dystrophy v0.53 UBAP1L Ee Ming Wong gene: UBAP1L was added
gene: UBAP1L was added to Cone-rod Dystrophy. Sources: Literature
Mode of inheritance for gene: UBAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBAP1L were set to PMID: 38293907; 38420906
Phenotypes for gene: UBAP1L were set to Cone-rod dystrophy (MONDO:0015993), UBAP1L-related
Review for gene: UBAP1L was set to GREEN
gene: UBAP1L was marked as current diagnostic
Added comment: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Mendeliome v1.1587 SLC12A9 Zornitza Stark Marked gene: SLC12A9 as ready
Mendeliome v1.1587 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1587 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Mendeliome v1.1587 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Genetic Epilepsy v0.2330 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2330 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 POP1 Ain Roesley Publications for gene: POP1 were set to
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Marked gene: CORIN as ready
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Mendeliome v1.1586 SNF8 Elena Savva Marked gene: SNF8 as ready
Mendeliome v1.1586 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Mendeliome v1.1586 SLC12A9 Zornitza Stark gene: SLC12A9 was added
gene: SLC12A9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A9 were set to 38334070
Phenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related
Review for gene: SLC12A9 was set to GREEN
Added comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopment phenotype, skeletal and brain abnormalities, hypopigmentation, dysmorphic features.
Sources: Literature
Callosome v0.518 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1586 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Mendeliome v1.1586 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Classified gene: CORIN as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Callosome v0.517 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Callosome v0.517 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Callosome v0.517 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5714 SLC12A9 Zornitza Stark gene: SLC12A9 was added
gene: SLC12A9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A9 were set to 38334070
Phenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related
Review for gene: SLC12A9 was set to GREEN
Added comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopmental phenotype, skeletal abnormalities, brain abnormalities, hypopigmentation, dysmorphic features.
Sources: Literature
Genetic Epilepsy v0.2329 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2329 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Callosome v0.517 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Callosome v0.517 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Marked gene: TUBA4A as ready
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Callosome v0.516 SNF8 Elena Savva Marked gene: SNF8 as ready
Callosome v0.516 SNF8 Elena Savva Gene: snf8 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Marked gene: SNF8 as ready
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2329 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2329 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.30 SNF8 Elena Savva Marked gene: SNF8 as ready
Optic Atrophy v1.30 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1585 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Aortopathy_Connective Tissue Disorders v1.80 THBS2 Chris Ciotta changed review comment from: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes was identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature; to: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature
Optic Atrophy v1.30 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Optic Atrophy v1.30 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.80 THBS2 Chris Ciotta gene: THBS2 was added
gene: THBS2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: THBS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THBS2 were set to PMID: 38433265
Phenotypes for gene: THBS2 were set to Ehlers-Danlos syndrome
Penetrance for gene: THBS2 were set to Complete
Review for gene: THBS2 was set to AMBER
Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes was identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature
Genetic Epilepsy v0.2328 SNF8 Elena Savva Marked gene: SNF8 as ready
Genetic Epilepsy v0.2328 SNF8 Elena Savva Gene: snf8 has been removed from the panel.
Fetal anomalies v1.200 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410
Skeletal dysplasia v0.272 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800
Mendeliome v1.1585 TUBA4A Seb Lunke Marked gene: TUBA4A as ready
Mendeliome v1.1585 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.199 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Mendeliome v1.1585 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Mendeliome v1.1585 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.272 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Skeletal Dysplasia_Fetal v0.219 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Fetal anomalies v1.198 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.29 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to AMBER
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Three of the patients (from two families) with the milder phenotype also have optic atrophy.

- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Skeletal dysplasia v0.271 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.218 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from to Schwartz-Jampel syndrome, type 1, MIM#255800; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139)
Genetic Epilepsy v0.2328 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to AMBER
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Two of the patients also had seizures.

- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1584 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.176 CORIN Daniel Flanagan gene: CORIN was added
gene: CORIN was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert list
Mode of inheritance for gene: CORIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CORIN were set to 37913506; 15637153
Phenotypes for gene: CORIN were set to ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Review for gene: CORIN was set to RED
Added comment: Two siblings with a homozygous loss-of-function variant in CORIN. Both presented with left atrial hypertrophic cardiomyopathy, hypertension, fibrosis, and arrhythmia isolated to the left atrium. A plasma sample obtained from one of the siblings had no detectable levels of corin.

One sibling also had a het variant, p.(Ser571Thr), in PKP2 (associated with AD ARVC). The PKP2 variant is LP/VUS in ClinVar.

Cor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Cor-/- mice also have spontaneous hypertension.
Sources: Expert list
Mendeliome v1.1584 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Review for gene: SNUPN was set to GREEN
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1584 APOLD1 Lucy Spencer gene: APOLD1 was added
gene: APOLD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOLD1 were set to 35638551
Phenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715)
Review for gene: APOLD1 was set to AMBER
Added comment: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature
Callosome v0.516 SNF8 Chern Lim edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Intellectual disability syndromic and non-syndromic v0.5713 SNF8 Chern Lim edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1584 RGS6 Seb Lunke Marked gene: RGS6 as ready
Mendeliome v1.1584 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Mendeliome v1.1584 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Bleeding and Platelet Disorders v1.27 APOLD1 Lucy Spencer gene: APOLD1 was added
gene: APOLD1 was added to Bleeding and Platelet Disorders. Sources: Literature
Mode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOLD1 were set to 35638551
Phenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715)
Review for gene: APOLD1 was set to AMBER
Added comment: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature
Skeletal Dysplasia_Fetal v0.217 HSPG2 Ain Roesley Marked gene: HSPG2 as ready
Skeletal Dysplasia_Fetal v0.217 HSPG2 Ain Roesley Gene: hspg2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5713 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Cataract v0.362 RGS6 Seb Lunke Marked gene: RGS6 as ready
Cataract v0.362 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Mendeliome v1.1583 TOGARAM2 Naomi Baker gene: TOGARAM2 was added
gene: TOGARAM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TOGARAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM2 were set to PMID:38374469
Phenotypes for gene: TOGARAM2 were set to Nonsyndromic genetic hearing loss (MONDO:0019497), TOGARAM2-related
Review for gene: TOGARAM2 was set to RED
Added comment: Paper reports one individual with bilateral profound hearing loss with a homozygous TOGARAM2 nonsense variant and demonstrated reduced mRNA expression in transfected cells.
Sources: Literature
Cataract v0.362 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Cataract. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.11 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Penetrance for gene: SNUPN were set to unknown
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1583 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Microcephaly v1.249 RGS6 Seb Lunke Marked gene: RGS6 as ready
Microcephaly v1.249 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5713 DENND5B Elena Savva Publications for gene: DENND5B were set to
Microcephaly v1.249 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Deafness_Isolated v1.54 TOGARAM2 Naomi Baker gene: TOGARAM2 was added
gene: TOGARAM2 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: TOGARAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM2 were set to PMID:38374469
Phenotypes for gene: TOGARAM2 were set to Nonsyndromic genetic hearing loss (MONDO:0019497), TOGARAM2-related
Review for gene: TOGARAM2 was set to RED
Added comment: Paper reports one individual with bilateral profound hearing loss with a homozygous TOGARAM2 nonsense variant and demonstrated reduced mRNA expression in transfected cells.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5713 DENND5B Elena Savva Mode of pathogenicity for gene: DENND5B was changed from None to None
Leukodystrophy - paediatric v0.306 DENND5B Elena Savva Publications for gene: DENND5B were set to
Mendeliome v1.1583 NIT1 Ain Roesley Marked gene: NIT1 as ready
Mendeliome v1.1583 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Mendeliome v1.1583 NIT1 Zornitza Stark Marked gene: NIT1 as ready
Mendeliome v1.1583 NIT1 Zornitza Stark Gene: nit1 has been classified as Green List (High Evidence).
Mendeliome v1.1583 NIT1 Ain Roesley Classified gene: NIT1 as Green List (high evidence)
Mendeliome v1.1583 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.26 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Penetrance for gene: SNUPN were set to unknown
Review for gene: SNUPN was set to GREEN
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1582 NIT1 Zornitza Stark Classified gene: NIT1 as Green List (high evidence)
Mendeliome v1.1582 NIT1 Zornitza Stark Gene: nit1 has been classified as Green List (High Evidence).
Callosome v0.516 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Callosome. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1581 NIT1 Paul De Fazio edited their review of gene: NIT1: Changed rating: GREEN
Mendeliome v1.1581 TUBA4A Sarah Pantaleo gene: TUBA4A was added
gene: TUBA4A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to PMID: 38413182
Phenotypes for gene: TUBA4A were set to Congenital myopathy MONDO:0019952
Review for gene: TUBA4A was set to AMBER
Added comment: One novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy.

Identified candidate genes using laser capture micro dissection, proteomics, WES, clinical data, myopathological changes, electrophysiological exams and thigh muscle MRIs.

The variant is de novo in both patients, c.679C>T, p.(Leu227Phe). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiqution-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of Leu227Phe resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model.

Patient 1 is 14yo and had delayed motor development milestones since infancy. Myopathic face, high-arched palate, waddling gait, winged scapula and muscle weakness in four limbs with lower extremities and proximal muscle more severely affected. Follow up at 14yo showed slight improvement in motor function compared with 3yo.

Patient 2 is 6yo and presented with motor retardation since birth. At 3yo, presented with mild ptosis and ophthalmoparesis, high-arched palate and muscle weakness involving both proximal and distal in all limbs.

No likely pathogenic variants in 116 other protein-encoding genes. Variants confirmed by Sanger sequencing and absent from gnomAD. ACMG predicts likely pathogenic classification.
Sources: Literature
Mendeliome v1.1581 DENND5B Elena Savva Publications for gene: DENND5B were set to
Intellectual disability syndromic and non-syndromic v0.5712 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1580 NIT1 Paul De Fazio gene: NIT1 was added
gene: NIT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIT1 were set to 38430071
Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057)
Penetrance for gene: NIT1 were set to unknown
gene: NIT1 was marked as current diagnostic
Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp).

Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings (honeycomb appearance of the basal ganglia-thalamus complex, due to numerous strongly dilated PVS). 3 patients had non-lobar intracerebral hemorrhage. Slowly progressive cognitive decline was also a key feature.

Metabolic analysis in urine confirmed loss of NIT1 enzymatic function.

Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients.
Sources: Literature
Mendeliome v1.1580 DENND5B Elena Savva reviewed gene: DENND5B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38387458; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DENND5B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Muscular dystrophy and myopathy_Paediatric v1.11 TUBA4A Sarah Pantaleo gene: TUBA4A was added
gene: TUBA4A was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to PMID: 38413182
Phenotypes for gene: TUBA4A were set to Congenital myopathy MONDO:0019952
Review for gene: TUBA4A was set to AMBER
Added comment: One novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy.

Identified candidate genes using laser capture micro dissection, proteomics, WES, clinical data, myopathological changes, electrophysiological exams and thigh muscle MRIs.

The variant is de novo in both patients, c.679C>T, p.(Leu227Phe). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiqution-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of Leu227Phe resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model.

Patient 1 is 14yo and had delayed motor development milestones since infancy. Myopathic face, high-arched palate, waddling gait, winged scapula and muscle weakness in four limbs with lower extremities and proximal muscle more severely affected. Follow up at 14yo showed slight improvement in motor function compared with 3yo.

Patient 2 is 6yo and presented with motor retardation since birth. At 3yo, presented with mild ptosis and ophthalmoparesis, high-arched palate and muscle weakness involving both proximal and distal in all limbs.

No likely pathogenic variants in 116 other protein-encoding genes. Variants confirmed by Sanger sequencing and absent from gnomAD. ACMG predicts likely pathogenic classification.
Sources: Literature
Dystonia - isolated/combined v1.37 NIT1 Ain Roesley Marked gene: NIT1 as ready
Dystonia - isolated/combined v1.37 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.37 NIT1 Ain Roesley Classified gene: NIT1 as Green List (high evidence)
Dystonia - isolated/combined v1.37 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Stroke v1.16 NIT1 Ain Roesley Marked gene: NIT1 as ready
Stroke v1.16 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Stroke v1.16 NIT1 Ain Roesley Classified gene: NIT1 as Green List (high evidence)
Stroke v1.16 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.36 NIT1 Paul De Fazio gene: NIT1 was added
gene: NIT1 was added to Dystonia - isolated/combined. Sources: Literature
Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIT1 were set to 38430071
Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057)
Penetrance for gene: NIT1 were set to unknown
Review for gene: NIT1 was set to GREEN
gene: NIT1 was marked as current diagnostic
Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp).

Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings. 3 patients had non-lobar intracerebral hemorrhage. Metabolic analysis in urine confirmed loss of NIT1 enzymatic function.

Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Marked gene: RREB1 as ready
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5711 POP1 Belinda Chong reviewed gene: POP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38351533; Phenotypes: Anauxetic dysplasia 2, MIM#617396; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal Dysplasia_Fetal v0.217 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5711 RREB1 Zornitza Stark gene: RREB1 was added
gene: RREB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to 32938917; 38332451
Phenotypes for gene: RREB1 were set to Rasopathy, MONDO:0021060, RREB1-related
Review for gene: RREB1 was set to AMBER
Added comment: PMID 32938917: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes. In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association.

PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.
Sources: Literature
Stroke v1.15 NIT1 Paul De Fazio gene: NIT1 was added
gene: NIT1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIT1 were set to 38430071
Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057)
Penetrance for gene: NIT1 were set to unknown
Review for gene: NIT1 was set to GREEN
gene: NIT1 was marked as current diagnostic
Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp).

Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings. 3 patients had non-lobar intracerebral hemorrhage. Metabolic analysis in urine confirmed loss of NIT1 enzymatic function.

Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients.
Sources: Literature
Rasopathy v0.102 RREB1 Zornitza Stark Phenotypes for gene: RREB1 were changed from Noonan syndrome-like disorder to Rasopathy, MONDO:0021060, RREB1-related
Rasopathy v0.101 RREB1 Zornitza Stark Publications for gene: RREB1 were set to 32938917
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Marked gene: FEZF2 as ready
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Classified gene: FEZF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Rasopathy v0.100 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Rasopathy v0.100 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Rasopathy v0.99 RREB1 Zornitza Stark edited their review of gene: RREB1: Added comment: PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.; Changed rating: AMBER; Changed publications: 32938917, 38332451; Changed phenotypes: Rasopathy, MONDO:0021060, RREB1-related
Intellectual disability syndromic and non-syndromic v0.5709 FEZF2 Ain Roesley gene: FEZF2 was added
gene: FEZF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FEZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEZF2 were set to 38425142
Phenotypes for gene: FEZF2 were set to neurodevelopmental disorder MONDO:0700092, FEZF2-related
Review for gene: FEZF2 was set to GREEN
gene: FEZF2 was marked as current diagnostic
Added comment: - 7 indiv but 1 has whole gene deletion and 6x SNV (4x PTCs and 2x same missense Arg344Cys)
- of the 6x SNV, 4x de novo + 1x from affected father
- all have ID/ASD
- 1x seizures
- 1x hypotonia
- 1x motor coordination disorder
- 2x enuresis after 7yo
Sources: Literature
Mendeliome v1.1580 FEZF2 Ain Roesley Marked gene: FEZF2 as ready
Mendeliome v1.1580 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Mendeliome v1.1580 RREB1 Zornitza Stark Publications for gene: RREB1 were set to 32938917
Mendeliome v1.1580 FEZF2 Ain Roesley Classified gene: FEZF2 as Green List (high evidence)
Mendeliome v1.1580 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Mendeliome v1.1579 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Mendeliome v1.1579 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1578 RREB1 Zornitza Stark edited their review of gene: RREB1: Added comment: PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.; Changed rating: AMBER; Changed publications: 32938917, 38332451; Changed phenotypes: Rasopathy, MONDO:0021060, RREB1-related
Mendeliome v1.1578 FEZF2 Ain Roesley gene: FEZF2 was added
gene: FEZF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FEZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEZF2 were set to 38425142
Phenotypes for gene: FEZF2 were set to neurodevelopmental disorder MONDO:0700092, FEZF2-related
Review for gene: FEZF2 was set to GREEN
gene: FEZF2 was marked as current diagnostic
Added comment: - 7 indiv but 1 has whole gene deletion and 6x SNV (4x PTCs and 2x same missense Arg344Cys)
- of the 6x SNV, 4x de novo + 1x from affected father
- all have ID/ASD
- 1x seizures
- 1x hypotonia
- 1x motor coordination disorder
- 2x enuresis after 7yo
Sources: Literature
Mendeliome v1.1577 ZFX Zornitza Stark Marked gene: ZFX as ready
Mendeliome v1.1577 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5708 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Neurodevelopmental disorder, MONDO:0700092, ZFX-related
Mendeliome v1.1577 ZFX Zornitza Stark Classified gene: ZFX as Green List (high evidence)
Mendeliome v1.1577 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Mendeliome v1.1576 ZFX Zornitza Stark gene: ZFX was added
gene: ZFX was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZFX were set to 26350204; 26740508; 38325380
Phenotypes for gene: ZFX were set to Neurodevelopmental disorder, MONDO:0700092, ZFX-related
Review for gene: ZFX was set to GREEN
Added comment: A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Marked gene: ZFX as ready
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Classified gene: ZFX as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Fetal anomalies v1.198 NARS Zornitza Stark reviewed gene: NARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM# 619091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v1.10 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Intellectual disability syndromic and non-syndromic v0.5706 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Genetic Epilepsy v0.2328 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Microcephaly v1.248 NARS Zornitza Stark reviewed gene: NARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM# 619091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1575 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Deafness_Isolated v1.54 STX4 Zornitza Stark Phenotypes for gene: STX4 were changed from Non-syndromic genetic hearing loss, MONDO:0019497, STX4-related to Deafness, autosomal recessive 123, MIM# 620745
Mendeliome v1.1575 STX4 Zornitza Stark Phenotypes for gene: STX4 were changed from Non-syndromic genetic hearing loss, MONDO:0019497, STX4-related. to Deafness, autosomal recessive 123, MIM# 620745
Mendeliome v1.1574 DES Zornitza Stark Mode of inheritance for gene: DES was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - complex v0.234 PAH Natalie Lim gene: PAH was added
gene: PAH was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAH were set to PMID: 25614310, PMID: 15390012, PMID: 30369906
Phenotypes for gene: PAH were set to Phenylketonuria MIM#261600
Review for gene: PAH was set to GREEN
Added comment: Reports of parkinsonism and dystonia have been documented as delayed manifestations amongst PKU patients although rare.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5706 ZFX Sarah Leigh gene: ZFX was added
gene: ZFX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZFX was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ZFX were set to 26350204; 26740508; 38325380
Phenotypes for gene: ZFX were set to X-linked neurodevelopmental disorder with recurrent facial gestalt
Review for gene: ZFX was set to GREEN
Added comment: To date, germline variants in ZFX have not been associated with a phenotype in OMIM or Gen2Phen.
A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Sources: Literature
Inflammatory bowel disease v0.118 ELF4 Peter McNaughton gene: ELF4 was added
gene: ELF4 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: ELF4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ELF4 were set to PMID: 38231408
Phenotypes for gene: ELF4 were set to Inflammatory bowel disease
Review for gene: ELF4 was set to GREEN
Added comment: Cohort of 14 patients from 13 families with many presenting with gastrointestinal inflammation and ulceration. Frequently patients had been labelled with IBD prior to diagnosis of ELF4.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5706 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732
Genetic Epilepsy v0.2328 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732
Mendeliome v1.1573 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516; Cutis laxa, intellectual disability, movement disorder to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732; Cutis laxa, intellectual disability, movement disorder
Genetic Epilepsy v0.2327 ALDH3A2 Zornitza Stark Mode of inheritance for gene: ALDH3A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1572 KLF14 Bryony Thompson Marked gene: KLF14 as ready
Mendeliome v1.1572 KLF14 Bryony Thompson Gene: klf14 has been classified as Red List (Low Evidence).
Mendeliome v1.1572 KLF14 Bryony Thompson Classified gene: KLF14 as Red List (low evidence)
Mendeliome v1.1572 KLF14 Bryony Thompson Gene: klf14 has been classified as Red List (Low Evidence).
Mendeliome v1.1571 NOTCH2NL Bryony Thompson Tag STR tag was added to gene: NOTCH2NL.
Mendeliome v1.1571 NLRP12 Bryony Thompson Publications for gene: NLRP12 were set to 18230725; 21360512; 24064030; 27633793
Fetal anomalies v1.198 THSD1 Zornitza Stark Marked gene: THSD1 as ready
Fetal anomalies v1.198 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.198 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Fetal anomalies v1.198 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.197 THSD1 Zornitza Stark gene: THSD1 was added
gene: THSD1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: THSD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THSD1 were set to 33569873; 27895300
Phenotypes for gene: THSD1 were set to Lymphatic malformation 13, MIM# 620244
Review for gene: THSD1 was set to GREEN
Added comment: PMID: 33569873 - 1 fetus with a homozygous PTC and nonimmune hydrops fetalis (NIHF), congenital heart disease and hemangiomas. FHx of 1/3 triplets with severe hydrops fetalis, not sequenced.
- Paper reviews previous NIHF cases and reports another homozygous PTC in two families ( and a recurring homozygous missense (p.Cys206Tyr) in three families.


PMID: 27895300- Mouse model has hydrocephaly with poor perfusion.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5705 CBL Hali Van Niel reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20694012, 20543203, 11315197; Phenotypes: CBL-related disorder MONDO:0013308; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 CACNA1A Hali Van Niel reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476654, 33985586; Phenotypes: developmental and epileptic encephalopathy, 42 MONDO:0014917; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 C12orf65 Hali Van Niel reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: None; Publications: 24284555, 20598281, 23188110, 24080142, PMID: 3479531; Phenotypes: hereditary spastic paraplegia 55 MONDO:0014020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BTD Hali Van Niel reviewed gene: BTD: Rating: GREEN; Mode of pathogenicity: None; Publications: 7550325, 9375914, 37751899, 32741581; Phenotypes: biotinidase deficiency MONDO:0009665; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BSCL2 Hali Van Niel reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12362029, 26072926, 28916377; Phenotypes: congenital generalized lipodystrophy type 2 MONDO:0010020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1570 PCSK2 Bryony Thompson Classified gene: PCSK2 as Red List (low evidence)
Mendeliome v1.1570 PCSK2 Bryony Thompson Gene: pcsk2 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.17 RFX6 Bryony Thompson changed review comment from: At least 3 unrelated cases with heterozygous variants and a suspected diagnosis of MODY. Null mouse model demonstrates abnormal pancreatic islet cells.
Sources: Expert list; to: At least 3 unrelated cases with heterozygous variants and a suspected diagnosis of MODY. Expected to have reduced penetrance. Null mouse model demonstrates abnormal pancreatic islet cells.
Sources: Expert list
Maturity-onset Diabetes of the Young v1.17 RFX6 Bryony Thompson edited their review of gene: RFX6: Changed rating: GREEN
Maturity-onset Diabetes of the Young v1.17 RFX6 Bryony Thompson Classified gene: RFX6 as Green List (high evidence)
Maturity-onset Diabetes of the Young v1.17 RFX6 Bryony Thompson Gene: rfx6 has been classified as Green List (High Evidence).
Maturity-onset Diabetes of the Young v1.16 RFX6 Bryony Thompson Phenotypes for gene: RFX6 were changed from Maturity-onset diabetes of the young to maturity-onset diabetes of the young MONDO:0018911
Maturity-onset Diabetes of the Young v1.15 WFS1 Bryony Thompson Publications for gene: WFS1 were set to 27185633
Maturity-onset Diabetes of the Young v1.14 RFX6 Bryony Thompson Publications for gene: RFX6 were set to 20148032; 25048417; 27185633; 29026101; 31001871
Maturity-onset Diabetes of the Young v1.13 RFX6 Bryony Thompson Classified gene: RFX6 as Amber List (moderate evidence)
Maturity-onset Diabetes of the Young v1.13 RFX6 Bryony Thompson Gene: rfx6 has been classified as Amber List (Moderate Evidence).
Maturity-onset Diabetes of the Young v1.12 RFX6 Bryony Thompson edited their review of gene: RFX6: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found heterozygous variants (mainly LoF) in RFX6 were ‘Inconclusive’ with being highly penetrant for diabetes (met one of two statistical criteria - met enrichment criteria & failed comparison to maximum credible allele frequency); Changed rating: AMBER; Changed publications: 20148032, 25048417, 27185633, 29026101, 31001871, 36208030
Intellectual disability syndromic and non-syndromic v0.5705 BCS1L Hali Van Niel reviewed gene: BCS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 9777342, 17314340, 11528392, 30582773, 30582773, 25914718; Phenotypes: Bjornstad syndrome MONDO:0009872; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCKDHB Hali Van Niel reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 7672509, 11509994, 14742428; Phenotypes: maple syrup urine disease type 1B MONDO:0023692; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCKDHA Hali Van Niel reviewed gene: BCKDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 7883996, 7672509, 34288399; Phenotypes: maple syrup urine disease type 1A MONDO:0023691; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS2 Hali Van Niel reviewed gene: BBS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11285252, 11567139; Phenotypes: Bardet-Biedl syndrome 2 MONDO:0014432; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS12 Hali Van Niel reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: 17160889, 20827784; Phenotypes: Bardet-Biedl syndrome 12 MONDO:0014440; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS10 Hali Van Niel reviewed gene: BBS10: Rating: GREEN; Mode of pathogenicity: None; Publications: 16582908, 20805367, 27245532; Phenotypes: Phenotype: Bardet-Biedl syndrome 10 MONDO:0014438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS1 Hali Van Niel reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12118255, 12677556, 12567324; Phenotypes: Bardet-Biedl syndrome 1 MONDO:0008854; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1569 RFX6 Bryony Thompson Added comment: Comment on mode of inheritance: Mitchell-Riley syndrome is AR and MODY is AD
Mendeliome v1.1569 RFX6 Bryony Thompson Mode of inheritance for gene: RFX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Maturity-onset Diabetes of the Young v1.12 WFS1 Bryony Thompson Marked gene: WFS1 as ready
Maturity-onset Diabetes of the Young v1.12 WFS1 Bryony Thompson Gene: wfs1 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.12 WFS1 Bryony Thompson Classified gene: WFS1 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.12 WFS1 Bryony Thompson Gene: wfs1 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.11 WFS1 Bryony Thompson reviewed gene: WFS1: Rating: RED; Mode of pathogenicity: None; Publications: 30014265, 36208030; Phenotypes: maturity-onset diabetes of the young MONDO:0018911; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1568 PPP2R2B Bryony Thompson Tag STR tag was added to gene: PPP2R2B.
Mendeliome v1.1568 SAMD12 Bryony Thompson Tag STR tag was added to gene: SAMD12.
Maturity-onset Diabetes of the Young v1.11 GATA6 Bryony Thompson Marked gene: GATA6 as ready
Maturity-onset Diabetes of the Young v1.11 GATA6 Bryony Thompson Gene: gata6 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.11 GATA6 Bryony Thompson Classified gene: GATA6 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.11 GATA6 Bryony Thompson Gene: gata6 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.50 APPL1 Bryony Thompson Publications for gene: APPL1 were set to 26073777
Monogenic Diabetes v0.49 APPL1 Bryony Thompson Classified gene: APPL1 as Red List (low evidence)
Monogenic Diabetes v0.49 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.48 APPL1 Bryony Thompson Deleted their comment
Monogenic Diabetes v0.48 APPL1 Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030
Mendeliome v1.1568 APPL1 Bryony Thompson Publications for gene: APPL1 were set to 26073777
Maturity-onset Diabetes of the Young v1.10 APPL1 Bryony Thompson Deleted their comment
Mendeliome v1.1567 APPL1 Bryony Thompson Classified gene: APPL1 as Red List (low evidence)
Mendeliome v1.1567 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Mendeliome v1.1566 APPL1 Bryony Thompson Deleted their comment
Mendeliome v1.1566 APPL1 Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030
Maturity-onset Diabetes of the Young v1.10 APPL1 Bryony Thompson Marked gene: APPL1 as ready
Maturity-onset Diabetes of the Young v1.10 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.10 APPL1 Bryony Thompson Publications for gene: APPL1 were set to 26073777
Maturity-onset Diabetes of the Young v1.9 APPL1 Bryony Thompson Classified gene: APPL1 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.9 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.8 APPL1 Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Marked gene: KLF11 as ready
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Publications for gene: KLF11 were set to 15774581; 26248217; 23589285; 31124255
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Classified gene: KLF11 as Red List (low evidence)
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search=
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.8 KLF11 Bryony Thompson Publications for gene: KLF11 were set to
Maturity-onset Diabetes of the Young v1.7 KLF11 Bryony Thompson Classified gene: KLF11 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.7 KLF11 Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search=
Maturity-onset Diabetes of the Young v1.7 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Mendeliome v1.1566 KLF11 Bryony Thompson Publications for gene: KLF11 were set to 15774581; 26248217; 23589285; 31124255
Mendeliome v1.1565 KLF11 Bryony Thompson Classified gene: KLF11 as Red List (low evidence)
Mendeliome v1.1565 KLF11 Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted
Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search=
Mendeliome v1.1565 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.6 SLC19A2 Bryony Thompson Marked gene: SLC19A2 as ready
Maturity-onset Diabetes of the Young v1.6 SLC19A2 Bryony Thompson Gene: slc19a2 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.6 SLC19A2 Bryony Thompson Classified gene: SLC19A2 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.6 SLC19A2 Bryony Thompson Gene: slc19a2 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.5 GATA6 Hali Van Niel gene: GATA6 was added
gene: GATA6 was added to Maturity-onset Diabetes of the Young. Sources: Other
Mode of inheritance for gene: GATA6 was set to Unknown
Publications for gene: GATA6 were set to 27185633
Review for gene: GATA6 was set to RED
Added comment: 1 patient with clinically diagnosed MODY with GATA6 variant
Sources: Other
Monogenic Diabetes v0.46 PPARG Hali Van Niel reviewed gene: PPARG: Rating: RED; Mode of pathogenicity: None; Publications: 30207237, 34900790; Phenotypes: diabetes mellitus MONDO:0005015; Mode of inheritance: Unknown
Maturity-onset Diabetes of the Young v1.5 WFS1 Hali Van Niel gene: WFS1 was added
gene: WFS1 was added to Maturity-onset Diabetes of the Young. Sources: Other
Mode of inheritance for gene: WFS1 was set to Unknown
Publications for gene: WFS1 were set to 27185633
Phenotypes for gene: WFS1 were set to maturity-onset diabetes of the young MONDO:0018911
Review for gene: WFS1 was set to RED
Added comment: 1 patient with clinically established MODY with WFS1 variant
Sources: Other
Maturity-onset Diabetes of the Young v1.5 SLC19A2 Hali Van Niel gene: SLC19A2 was added
gene: SLC19A2 was added to Maturity-onset Diabetes of the Young. Sources: Other
Mode of inheritance for gene: SLC19A2 was set to Unknown
Publications for gene: SLC19A2 were set to 27185633
Phenotypes for gene: SLC19A2 were set to maturity-onset diabetes of the young MONDO:0018911
Review for gene: SLC19A2 was set to RED
Added comment: 1 patient with clinically established MODY with SLC19A2 variant
Sources: Other
Mendeliome v1.1564 KLF14 Hali Van Niel changed review comment from: PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other; to: Cannot find any evidence of association with mendelian disease

PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other
Mendeliome v1.1564 KLF14 Hali Van Niel gene: KLF14 was added
gene: KLF14 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: KLF14 was set to Unknown
Publications for gene: KLF14 were set to 33389382; 35081256; 24486580
Phenotypes for gene: KLF14 were set to diabetes mellitus MONDO:0005015
Review for gene: KLF14 was set to RED
Added comment: PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other
Mendeliome v1.1564 PCSK2 Hali Van Niel gene: PCSK2 was added
gene: PCSK2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: PCSK2 was set to Unknown
Publications for gene: PCSK2 were set to 26607656; 7698505; 17618154
Phenotypes for gene: PCSK2 were set to diabetes mellitus MONDO:0005015
Review for gene: PCSK2 was set to RED
Added comment: Cannot find any evidence of association with mendelian disease

PMID: 26607656

10 SNPs genotyped, genetic polymorphisms responsible for glucose homeostasis and incidental diabetes

PMID: 7698505
DNA polymorphism found in 11% of non insulin dependent diabetes patients (out of 152 japanese patients) vs 4% in health population (out of 102 japanese patients).

PMID: 17618154
29 SNPS analysed across PCSK2, 4 SNPS associated type 2 diabetes in african american population
Sources: Other
Mendeliome v1.1564 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 22405087; 25351951; 30689204; 32519519; 25351951
Mendeliome v1.1563 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Optic Atrophy v1.29 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 25351951; 22405087
Optic Atrophy v1.28 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mitochondrial disease v0.918 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 22405087; 25351951; 30689204; 32519519; 25351951
Mitochondrial disease v0.917 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Marked gene: TSEN34 as ready
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Added comment: Comment when marking as ready: No publications specifically reporting seizures identified.
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Marked gene: TSEN34 as ready
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2326 WDFY3 Zornitza Stark Phenotypes for gene: WDFY3 were changed from ?Microcephaly 18, primary, autosomal dominant MIM#617520 to Microcephaly 18, primary, autosomal dominant MIM#617520
Mendeliome v1.1562 YEATS2 Zornitza Stark Tag STR tag was added to gene: YEATS2.
Genetic Epilepsy v0.2325 YEATS2 Zornitza Stark Tag STR tag was added to gene: YEATS2.
Genetic Epilepsy v0.2325 ZMIZ1 Zornitza Stark Classified gene: ZMIZ1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2325 ZMIZ1 Zornitza Stark Gene: zmiz1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2324 ZMIZ1 Zornitza Stark reviewed gene: ZMIZ1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies MIM#618659; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Marked gene: ZSWIM6 as ready
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Gene: zswim6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Classified gene: ZSWIM6 as Green List (high evidence)
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Gene: zswim6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2323 ZSWIM6 Elena Savva gene: ZSWIM6 was added
gene: ZSWIM6 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZSWIM6 were set to PMID: 29198722; 33958584
Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis MIM#603671; Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features MIM#617865
Review for gene: ZSWIM6 was set to GREEN
Added comment: Seizures listed in OMIM as a feature of both conditions.

PMID: 29198722 - seven unrelated individuals with a recurrent de novo nonsense variant p.Arg913* in the penultimate exon. 4/7 confirmed to have seizures or possible seizures.

PMID: 33958584 - Japanese male patient with severe neurodevelopmental delay, epilepsy, distinctive facial features, microcephaly, growth deficiency, abnormal behavior, and frequent vomiting but without frontonasal or limb malformations. Proband had the same de novo p.Arg913* variant
Sources: Literature
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva Marked gene: ZMIZ1 as ready
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva Gene: zmiz1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva gene: ZMIZ1 was added
gene: ZMIZ1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZMIZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZMIZ1 were set to PMID: 30639322
Phenotypes for gene: ZMIZ1 were set to Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies MIM#618659
Review for gene: ZMIZ1 was set to RED
Added comment: Seizures (rare) listed in OMIM

PMID: 30639322 - gene-disease establishing paper. Cohort of 19 probands (16 unrelated), where 3 were reported with seizures.
Sources: Literature
Genetic Epilepsy v0.2321 ZIC2 Elena Savva Marked gene: ZIC2 as ready
Genetic Epilepsy v0.2321 ZIC2 Elena Savva Gene: zic2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2321 ZIC2 Elena Savva gene: ZIC2 was added
gene: ZIC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZIC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ZIC2 were set to Holoprosencephaly 5 MIM#609637
Review for gene: ZIC2 was set to RED
Added comment: No evidence of SNVs in this gene causing epilepsy/seizures.

This gene was listed in the Oliver list.
Sources: Literature
Genetic Epilepsy v0.2320 YEATS2 Elena Savva Marked gene: YEATS2 as ready
Genetic Epilepsy v0.2320 YEATS2 Elena Savva Gene: yeats2 has been classified as Red List (Low Evidence).
Mendeliome v1.1562 YEATS2 Elena Savva Marked gene: YEATS2 as ready
Mendeliome v1.1562 YEATS2 Elena Savva Gene: yeats2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2320 YEATS2 Elena Savva gene: YEATS2 was added
gene: YEATS2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: YEATS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YEATS2 were set to PMID: 22713812; 31539032
Phenotypes for gene: YEATS2 were set to ?Epilepsy, myoclonic, familial adult, 4 MIM#615127
Review for gene: YEATS2 was set to RED
Added comment: PMID: 22713812 - 13 members of a single family with Benign Adult Familial Myoclonic Epilepsy (BAFME). The average age of onset was 19.5 (range 10–33) years for tremor and 25 (range 19–33) years for seizures.
PMID: 31539032 - Expansions of TTTTA and insertions of TTTCA repeats in intron 1 of YEATS2 segregated in the same family ^.
Sources: Literature
Mendeliome v1.1562 YEATS2 Elena Savva gene: YEATS2 was added
gene: YEATS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YEATS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YEATS2 were set to PMID: 22713812; 31539032
Phenotypes for gene: YEATS2 were set to ?Epilepsy, myoclonic, familial adult, 4 MIM#615127
Review for gene: YEATS2 was set to RED
Added comment: PMID: 22713812 - 13 members of a single family with Benign Adult Familial Myoclonic Epilepsy (BAFME). The average age of onset was 19.5 (range 10–33) years for tremor and 25 (range 19–33) years for seizures.
PMID: 31539032 - Expansions of TTTTA and insertions of TTTCA repeats in intron 1 of YEATS2 segregated in the same family ^.
Sources: Literature
Genetic Epilepsy v0.2319 XPR1 Elena Savva Marked gene: XPR1 as ready
Genetic Epilepsy v0.2319 XPR1 Elena Savva Gene: xpr1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2319 XPR1 Elena Savva Classified gene: XPR1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2319 XPR1 Elena Savva Gene: xpr1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2318 XPR1 Elena Savva gene: XPR1 was added
gene: XPR1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: XPR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: XPR1 were set to PMID: 33433330
Phenotypes for gene: XPR1 were set to Basal ganglia calcification, idiopathic, 6 MIM#616413
Review for gene: XPR1 was set to AMBER
Added comment: Seizures (in some patients) listed in OMIM

PMID: 33433330
- chet proband (PTC, missense) with paroxysmal kinesigenic dyskinesia with infantile convulsions, and generalized tonic-clonic seizures (GTCS) at the age of 2 years. Both parents were unaffected.
- Only missense in AD disease had been reported.
- Reviews literature, notes seizures 2/12 unrelated individuals, where an additional proband was ?seizures?
Sources: Literature
Genetic Epilepsy v0.2317 WDFY3 Elena Savva Marked gene: WDFY3 as ready
Genetic Epilepsy v0.2317 WDFY3 Elena Savva Gene: wdfy3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2317 WDFY3 Elena Savva gene: WDFY3 was added
gene: WDFY3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WDFY3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WDFY3 were set to PMID: 31327001
Phenotypes for gene: WDFY3 were set to ?Microcephaly 18, primary, autosomal dominant MIM#617520
Review for gene: WDFY3 was set to RED
Added comment: PMID: 31327001 - cohort of 13 probands and mouse model, NONE had reported to have epilepsy/seizures.

Gene was listed as part of the Oliver review for genes associated with epilepsy
Sources: Literature
Genetic Epilepsy v0.2316 WASHC4 Elena Savva Marked gene: WASHC4 as ready
Genetic Epilepsy v0.2316 WASHC4 Elena Savva Gene: washc4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2316 WASHC4 Elena Savva gene: WASHC4 was added
gene: WASHC4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WASHC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASHC4 were set to PMID: 34599609
Phenotypes for gene: WASHC4 were set to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Review for gene: WASHC4 was set to RED
Added comment: PMID: 34599609 - two siblings, only 1 sibling presented with epilepsy with generalized tonic–clonic seizures and received oxcarbazepine (seizure-free on therapy). They were homozygous for a missense, some functional studies supporting pathogenicity.
Review of previous reports did NOT describe any other reports of seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5705 WASHC4 Elena Savva Phenotypes for gene: WASHC4 were changed from ?Mental retardation, autosomal recessive 43; OMIM #615817 to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Mendeliome v1.1561 WASHC4 Elena Savva Phenotypes for gene: WASHC4 were changed from Mental retardation, autosomal recessive 43, MIM #615817 to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Genetic Epilepsy v0.2315 WAC Elena Savva Marked gene: WAC as ready
Genetic Epilepsy v0.2315 WAC Elena Savva Gene: wac has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2315 WAC Elena Savva Classified gene: WAC as Green List (high evidence)
Genetic Epilepsy v0.2315 WAC Elena Savva Gene: wac has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2314 WAC Elena Savva gene: WAC was added
gene: WAC was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WAC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WAC were set to PMID: 36420948
Phenotypes for gene: WAC were set to Desanto-Shinawi syndrome MIM#616708
Review for gene: WAC was set to GREEN
Added comment: Seizures (in some patients) listed in OMIM

PMID: 36420948 - reviews literature, describes seizures in 10/33 probands
Sources: Literature
Mendeliome v1.1560 UGGT1 Elena Savva Marked gene: UGGT1 as ready
Mendeliome v1.1560 UGGT1 Elena Savva Gene: uggt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2313 UGGT1 Elena Savva Marked gene: UGGT1 as ready
Genetic Epilepsy v0.2313 UGGT1 Elena Savva Gene: uggt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2313 UGGT1 Elena Savva gene: UGGT1 was added
gene: UGGT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UGGT1 was set to Unknown
Review for gene: UGGT1 was set to RED
Added comment: Gene was on the Oliver list for epilepsy genes.

No gene-disease association paper has been published.

GnomAD NOT constrained for LOF variants.
Sources: Literature
Mendeliome v1.1560 UGGT1 Elena Savva gene: UGGT1 was added
gene: UGGT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UGGT1 was set to Unknown
Review for gene: UGGT1 was set to RED
Added comment: Gene was on the Oliver list for epilepsy genes.

No gene-disease association paper has been published.

GnomAD NOT constrained for LOF variants.
Sources: Literature
Genetic Epilepsy v0.2312 UBTF Elena Savva Classified gene: UBTF as Amber List (moderate evidence)
Genetic Epilepsy v0.2312 UBTF Elena Savva Gene: ubtf has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2312 UBTF Elena Savva Classified gene: UBTF as Amber List (moderate evidence)
Genetic Epilepsy v0.2312 UBTF Elena Savva Gene: ubtf has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2311 UBTF Elena Savva Marked gene: UBTF as ready
Genetic Epilepsy v0.2311 UBTF Elena Savva Gene: ubtf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2311 UBTF Elena Savva gene: UBTF was added
gene: UBTF was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBTF were set to PMID: 30517966
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Review for gene: UBTF was set to AMBER
Added comment: PMID: 30517966 - recurring de novo missense p.Glu210Lys, observed in 11 probands with neurodegeneration. 3/11 had seizures. Paper had an additional proband with this variant and drug-resistant epilepsy.
Sources: Literature
Fetal anomalies v1.196 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Autosomal Dominant Coloboma to Microphthalmia/coloboma 11, MIM# 620731
Fetal anomalies v1.195 FZD5 Zornitza Stark Classified gene: FZD5 as Amber List (moderate evidence)
Fetal anomalies v1.195 FZD5 Zornitza Stark Gene: fzd5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.194 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed rating: AMBER
Fetal anomalies v1.194 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Mendeliome v1.1559 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Coloboma MONDO:0001476 to Microphthalmia/coloboma 11, MIM# 620731
Mendeliome v1.1558 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Anophthalmia_Microphthalmia_Coloboma v1.39 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Coloboma (MONDO:0001476), FZD5-related to Microphthalmia/coloboma 11, MIM# 620731
Anophthalmia_Microphthalmia_Coloboma v1.38 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Metal Metabolism Disorders v0.37 STAB1 Zornitza Stark Phenotypes for gene: STAB1 were changed from Iron metabolism metabolism, MONDO:0002279, STAB1-related; Hyperferritinaemia without iron overload to Hyperferritinemia, MIM# 620729
Metal Metabolism Disorders v0.36 STAB1 Zornitza Stark reviewed gene: STAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperferritinemia, MIM# 620729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1558 STAB1 Zornitza Stark Phenotypes for gene: STAB1 were changed from Iron metabolism disease (MONDO:0002279), STAB1-related to Hyperferritinemia, MIM# 620729
Mendeliome v1.1557 STAB1 Zornitza Stark reviewed gene: STAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperferritinemia, MIM# 620729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.234 NAA15 Shekeeb Mohammad gene: NAA15 was added
gene: NAA15 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: NAA15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NAA15 were set to 38380600
Phenotypes for gene: NAA15 were set to dystonia; neurodevelopmental delay
Penetrance for gene: NAA15 were set to unknown
Review for gene: NAA15 was set to GREEN
Added comment: previous 3 cases in literature referenced in 38380600
Sources: Literature
Genetic Epilepsy v0.2310 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719; Spinocerebellar ataxia 47, MIM# 617931 to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5704 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM#617931; intellectual disability; epilepsy to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Spinocerebellar ataxia 47, MIM#617931, Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Genetic Epilepsy v0.2309 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from intellectual disability; epilepsy; Spinocerebellar ataxia 47, MIM# 617931 to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719; Spinocerebellar ataxia 47, MIM# 617931
Genetic Epilepsy v0.2308 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Mendeliome v1.1557 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder, MONDO:0700092, PUM1-related to Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Mendeliome v1.1556 PUM1 Zornitza Stark Publications for gene: PUM1 were set to 29474920; 25768905; 30903679; 31859446
Mendeliome v1.1555 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Spinocerebellar ataxia 47, MIM# 617931, Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Genetic Epilepsy v0.2308 TWNK Elena Savva Classified gene: TWNK as Green List (high evidence)
Genetic Epilepsy v0.2308 TWNK Elena Savva Gene: twnk has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2307 TWNK Elena Savva Marked gene: TWNK as ready
Genetic Epilepsy v0.2307 TWNK Elena Savva Gene: twnk has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2307 TWNK Elena Savva gene: TWNK was added
gene: TWNK was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TWNK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TWNK were set to PMID: 19304794
Phenotypes for gene: TWNK were set to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) MIM#271245; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286
Review for gene: TWNK was set to GREEN
Added comment: PMID: 19304794 - reviews, notes epilepsia partialis continua occurred in 15 patients leading to generalized epileptic statuses in 13/15. Probands had biallelic variants

OMIM lists Seizures (uncommon) as a phenotype for AD disease
Sources: Literature
Genetic Epilepsy v0.2306 TSEN34 Elena Savva gene: TSEN34 was added
gene: TSEN34 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TSEN34 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSEN34 were set to Pontocerebellar hypoplasia type 2C, MIM#612390
Review for gene: TSEN34 was set to RED
Added comment: Gene was part of the Oliver list, no new publications
Sources: Literature
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Marked gene: TSEN15 as ready
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Gene: tsen15 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Classified gene: TSEN15 as Amber List (moderate evidence)
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Gene: tsen15 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2304 TSEN15 Elena Savva gene: TSEN15 was added
gene: TSEN15 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TSEN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN15 were set to PMID: 27392077
Phenotypes for gene: TSEN15 were set to Pontocerebellar hypoplasia, type 2F MIM#617026
Review for gene: TSEN15 was set to AMBER
Added comment: Few patients reported with disease for this gene

PMID: 27392077 - 2/4 probands had seizures, onset <1 year old. Probands had homozygous missense, none had homs in v4 gnomAD. Functional studies support missense pathogenicity.
Sources: Literature
Mitochondrial disease v0.916 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Optic Atrophy v1.27 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1555 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2303 TRMT1 Elena Savva Classified gene: TRMT1 as Green List (high evidence)
Genetic Epilepsy v0.2303 TRMT1 Elena Savva Gene: trmt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2302 TRMT1 Elena Savva Classified gene: TRMT1 as Green List (high evidence)
Genetic Epilepsy v0.2302 TRMT1 Elena Savva Gene: trmt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2301 TRMT1 Elena Savva Marked gene: TRMT1 as ready
Genetic Epilepsy v0.2301 TRMT1 Elena Savva Gene: trmt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2301 TRMT1 Elena Savva gene: TRMT1 was added
gene: TRMT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT1 were set to PMID: 31898845; 26308914; 30289604
Phenotypes for gene: TRMT1 were set to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Review for gene: TRMT1 was set to GREEN
Added comment: Rarely reported gene

Seizures (in some patients) described in OMIM.

PMID: 31898845 - homozygous missense in a proband with developmental delay, ID, and epilepsy. Functional studies support pathogenicity of the missense.

PMID: 26308914 - family with a homozygous PTC. The patients did not manifest any other neurological problems, ie. NO seizures.

PMID: 30289604 - two families (total 4 affected) with hom PTC and canonical splice. All had seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5703 TRMT1 Elena Savva Phenotypes for gene: TRMT1 were changed from Mental retardation, autosomal recessive 68; OMIM #618302 to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Mendeliome v1.1555 TRMT1 Elena Savva Phenotypes for gene: TRMT1 were changed from Mental retardation, autosomal recessive 68; OMIM #618302 to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Marked gene: TRIT1 as ready
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Gene: trit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Classified gene: TRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Gene: trit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2299 TRIT1 Elena Savva gene: TRIT1 was added
gene: TRIT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIT1 were set to PMID: 36047296; 36049610
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35 MIM#617873
Review for gene: TRIT1 was set to GREEN
Added comment: PMID: 36047296 - two probands with tonic–clonic seizures, as well as myoclonic seizures in patient 1. Both probands had chet PTC/missense.

PMID: 36049610 - two probands with seizures. Both probands had chet PTC/missense. Reviews, seizures reported in 100% (20/20) patients, including myoclonic epilepsy and febrile convulsions
Sources: Literature
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Marked gene: TRIP12 as ready
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Gene: trip12 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Classified gene: TRIP12 as Amber List (moderate evidence)
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Gene: trip12 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2297 TRIP12 Elena Savva gene: TRIP12 was added
gene: TRIP12 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIP12 were set to PMID: 36275919; 32424948
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49 MIM#617752
Review for gene: TRIP12 was set to AMBER
Added comment: Seizures described as a rare feature in OMIM

PMID: 36275919 - patient with GDD, hypotonia and intermittent seizures. De novo synonymous variant with proven splice outcome found.

PMID: 32424948 - reviews, epilepsy observed in 21% (5/24) patients
Sources: Literature
Genetic Epilepsy v0.2296 TRIO Elena Savva Classified gene: TRIO as Green List (high evidence)
Genetic Epilepsy v0.2296 TRIO Elena Savva Gene: trio has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2295 TRIO Elena Savva Marked gene: TRIO as ready
Genetic Epilepsy v0.2295 TRIO Elena Savva Gene: trio has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2295 TRIO Elena Savva gene: TRIO was added
gene: TRIO was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIO was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TRIO were set to Intellectual developmental disorder, autosomal dominant 44, with microcephaly MIM#617061; Intellectual developmental disorder, autosomal dominant 63, with macrocephaly MIM#618825
Review for gene: TRIO was set to GREEN
Added comment: Seizures described in OMIM as a rare feature of both AR and AD disease

GeneReviews: seizures described in 7/19 probands with GOF variants, and 7/29 in individuals with LOF variants. Only one in ten individuals with a TRIO missense variant in the GEFD1 domain had seizures
Sources: Literature
Genetic Epilepsy v0.2294 TREM2 Elena Savva Classified gene: TREM2 as Green List (high evidence)
Genetic Epilepsy v0.2294 TREM2 Elena Savva Gene: trem2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2294 TREM2 Elena Savva Classified gene: TREM2 as Green List (high evidence)
Genetic Epilepsy v0.2294 TREM2 Elena Savva Gene: trem2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2293 TREM2 Elena Savva Marked gene: TREM2 as ready
Genetic Epilepsy v0.2293 TREM2 Elena Savva Gene: trem2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2293 TREM2 Elena Savva gene: TREM2 was added
gene: TREM2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TREM2 were set to PMID: 36820836; 24910390
Phenotypes for gene: TREM2 were set to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 MIM#618193
Review for gene: TREM2 was set to GREEN
Added comment: PMID: 36820836 - adult with repetitive seizures with a homozygous missense variant. Sibling also affected. No functional studies.

PMID: 24910390 - two siblings with a hom missense, no seizures reported. Summary of literature notes epilepsy in 75% of probands.

Seizures listed in OMIM
Sources: Literature
Genetic Epilepsy v0.2292 TPK1 Elena Savva Marked gene: TPK1 as ready
Genetic Epilepsy v0.2292 TPK1 Elena Savva Gene: tpk1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2292 TPK1 Elena Savva Classified gene: TPK1 as Green List (high evidence)
Genetic Epilepsy v0.2292 TPK1 Elena Savva Gene: tpk1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2291 TPK1 Elena Savva gene: TPK1 was added
gene: TPK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPK1 were set to PMID: 37622082
Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458
Review for gene: TPK1 was set to GREEN
Added comment: PMID: 37622082
- proband 1 had a single convulsive seizure after fever, rashes. Diagnosed with leigh syndrome. Was chet for a PTC and missense.
- proband 2 had frequent tonic seizures, Was chet for a PTC and missense.
Review of literature found seizure (10/28, 35.71%) of reported cases
Sources: Literature
Neurodegeneration with brain iron accumulation v0.32 Bryony Thompson Panel name changed from Neuroferritinopathies to Neurodegeneration with brain iron accumulation
Early-onset Parkinson disease v0.294 FTL Bryony Thompson Publications for gene: FTL were set to 23447832; 20301320
Early-onset Parkinson disease v0.293 FTL Bryony Thompson Publications for gene: FTL were set to
Early-onset Parkinson disease v0.292 FTL Bryony Thompson Mode of inheritance for gene: FTL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Classified gene: FTL as Green List (high evidence)
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Added comment: Comment on list classification: Parkinsonism can be a presenting feature of the condition
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Gene: ftl has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Classified gene: FTL as Green List (high evidence)
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Added comment: Comment on list classification: Parkinsonism can be a presenting feature of the condition
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Gene: ftl has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.290 TAF1 Bryony Thompson Tag STR tag was added to gene: TAF1.
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Marked gene: FBXO7 as ready
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Gene: fbxo7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Publications for gene: FBXO7 were set to
Early-onset Parkinson disease v0.289 FBXO7 Bryony Thompson Phenotypes for gene: FBXO7 were changed from to parkinsonian-pyramidal syndrome MONDO:0009830
Early-onset Parkinson disease v0.288 FBXO7 Bryony Thompson Mode of inheritance for gene: FBXO7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Marked gene: DNAJC6 as ready
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Gene: dnajc6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Phenotypes for gene: DNAJC6 were changed from to juvenile onset Parkinson disease 19A MONDO:0014231
Early-onset Parkinson disease v0.286 DNAJC6 Bryony Thompson Publications for gene: DNAJC6 were set to
Early-onset Parkinson disease v0.285 DNAJC6 Bryony Thompson Mode of inheritance for gene: DNAJC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Marked gene: DCTN1 as ready
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Gene: dctn1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Phenotypes for gene: DCTN1 were changed from Perry syndrome MONDO:0008201 to Perry syndrome MONDO:0008201
Early-onset Parkinson disease v0.283 DCTN1 Bryony Thompson Phenotypes for gene: DCTN1 were changed from to Perry syndrome MONDO:0008201
Early-onset Parkinson disease v0.282 DCTN1 Bryony Thompson Publications for gene: DCTN1 were set to 20945553
Early-onset Parkinson disease v0.282 DCTN1 Bryony Thompson Publications for gene: DCTN1 were set to
Early-onset Parkinson disease v0.281 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.281 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Classified gene: DCTN1 as Green List (high evidence)
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a characteristic feature of Perry syndrome
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Gene: dctn1 has been classified as Green List (High Evidence).
Fetal anomalies v1.194 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Fetal anomalies v1.193 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176
Fetal anomalies v1.192 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: Single family with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100
Clefting disorders v0.252 NEK1 Zornitza Stark Marked gene: NEK1 as ready
Clefting disorders v0.252 NEK1 Zornitza Stark Gene: nek1 has been classified as Green List (High Evidence).
Clefting disorders v0.252 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from SHORT-RIB THORACIC DYSPLASIA 6 WITH OR WITHOUT POLYDACTYLY; SRTD6 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Clefting disorders v0.251 NEK1 Zornitza Stark Publications for gene: NEK1 were set to
Clefting disorders v0.250 NEK1 Zornitza Stark reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211617, 22499340, 25492405, 28123176, 27530628; Phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1554 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Mendeliome v1.1553 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176; 33445179
Mendeliome v1.1552 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: PMID 27530628: two brothers with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100, Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Ciliopathies v1.51 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Ciliopathies v1.50 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176
Ciliopathies v1.49 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: PMID 27530628: two brothers with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100
Mendeliome v1.1552 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000 to Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000; Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Mendeliome v1.1551 HMBS Zornitza Stark edited their review of gene: HMBS: Changed phenotypes: Porphyria, acute intermittent, MIM#176000, Porphyria, acute intermittent, non-erythroid variant, MIM#176000, Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711
Regression v0.544 HMBS Zornitza Stark Marked gene: HMBS as ready
Regression v0.544 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Regression v0.544 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from to Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Regression v0.543 HMBS Zornitza Stark Mode of inheritance for gene: HMBS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.542 HMBS Zornitza Stark reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Marked gene: HMBS as ready
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Publications for gene: HMBS were set to 15534187
Intellectual disability syndromic and non-syndromic v0.5701 HMBS Zornitza Stark Classified gene: HMBS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5701 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5700 HMBS Zornitza Stark edited their review of gene: HMBS: Changed publications: 15534187, 34089223; Changed phenotypes: Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711
Intellectual disability syndromic and non-syndromic v0.5700 HMBS Zornitza Stark gene: HMBS was added
gene: HMBS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 15534187
Phenotypes for gene: HMBS were set to Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Review for gene: HMBS was set to GREEN
Added comment: Several families reported with encephalopathy/leukoencephalopathy and ballelic variants in this gene.
Sources: Expert Review
Leukodystrophy - paediatric v0.305 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, MIM#176000; Acute intermittent porphyria-related leukoencephalopathy to Leukoencephalopathy, porphyria-related, MIM# 620711
Leukodystrophy - paediatric v0.304 HMBS Zornitza Stark edited their review of gene: HMBS: Changed phenotypes: Leukoencephalopathy, porphyria-related, MIM# 620711
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni edited their review of gene: DDX3X: Changed publications: PMID: 32135084, 32852922
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni changed review comment from: Genotype-Phenotype Correlations

Females. Affected females with a subset of missense variants generally are more severely affected than those with truncating variants [Lennox et al 2020].

Polymicrogyria has been associated with missense or in-frame deletions [Lennox et al 2020].

Males. While all affected males have had missense DDX3X variants (see Table 6), their female relatives who are heterozygous for the same DDX3X variant do not manifest an atypical neurodevelopmental phenotype.; to: Genotype-Phenotype Correlations

Females. Affected females with a subset of missense variants generally are more severely affected than those with truncating variants PMID: 32135084

Polymicrogyria has been associated with missense or in-frame deletions PMID: 32135084

Males. While all affected males have had missense DDX3X variants , their female relatives who are heterozygous for the same DDX3X variant do not manifest an atypical neurodevelopmental phenotype.
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni commented on gene: DDX3X
Mendeliome v1.1551 LCP2 Achchuthan Shanmugasundram reviewed gene: LCP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37211057; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.172 MYO3A Zornitza Stark Phenotypes for gene: MYO3A were changed from Deafness, autosomal recessive 30, MIM# 607101; dominant deafness to Deafness, autosomal recessive 30, MIM# 607101; Deafness, autosomal dominant 90, MIM# 620722
Deafness_IsolatedAndComplex v1.171 MYO3A Zornitza Stark edited their review of gene: MYO3A: Changed phenotypes: Deafness, autosomal recessive 30, MIM# 607101, Deafness, autosomal dominant 90, MIM# 620722
Mendeliome v1.1551 MYO3A Zornitza Stark Phenotypes for gene: MYO3A were changed from Deafness, autosomal recessive 30 OMIM:607101; autosomal recessive nonsyndromic deafness 30 MONDO:0011774; dominant deafness to Deafness, autosomal recessive 30, MIM# 607101; Deafness, autosomal dominant 90, MIM# 620722
Mendeliome v1.1550 MYO3A Zornitza Stark edited their review of gene: MYO3A: Changed phenotypes: Deafness, autosomal recessive 30, MIM# 607101, Deafness, autosomal dominant 90, MIM# 620722
Deafness_Isolated v1.53 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness to Deafness, autosomal dominant; Deafness, autosomal recessive 122, MIM# 620714
Deafness_Isolated v1.52 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to 29671961; 27311106
Deafness_Isolated v1.51 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_Isolated v1.50 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Added comment: Single family reported with bi-allelic variants. Mouse model.; Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal dominant, Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.171 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness, autosomal dominant to Deafness, autosomal dominant; Deafness, autosomal recessive 122, MIM# 620714
Deafness_IsolatedAndComplex v1.170 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to
Deafness_IsolatedAndComplex v1.169 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.168 TMTC2 Zornitza Stark commented on gene: TMTC2: Single family reported with bi-allelic variants. Mouse model.
Deafness_IsolatedAndComplex v1.168 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1550 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness to Deafness, autosomal recessive 122, MIM# 620714
Mendeliome v1.1549 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to 29671961; 27311106
Mendeliome v1.1548 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1547 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Added comment: Single family reported with bi-allelic variants.

Mouse model.; Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autism v0.196 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Autism v0.196 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Autism v0.196 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Mendeliome v1.1547 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Mendeliome v1.1547 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Mendeliome v1.1547 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Marked gene: CSF1R as ready
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Gene: csf1r has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Phenotypes for gene: CSF1R were changed from to leukoencephalopathy, diffuse hereditary, with spheroids 1 MONDO:0800027
Early-onset Parkinson disease v0.278 CSF1R Bryony Thompson Publications for gene: CSF1R were set to
Early-onset Parkinson disease v0.277 CSF1R Bryony Thompson Mode of inheritance for gene: CSF1R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Classified gene: CSF1R as Green List (high evidence)
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Added comment: Comment on list classification: Parkinsonian signs can be a feature on the condition
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Gene: csf1r has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Marked gene: C19orf12 as ready
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Gene: c19orf12 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Phenotypes for gene: C19orf12 were changed from to neurodegeneration with brain iron accumulation 4 MONDO:0013674
Early-onset Parkinson disease v0.274 C19orf12 Bryony Thompson Publications for gene: C19orf12 were set to
Early-onset Parkinson disease v0.273 C19orf12 Bryony Thompson Mode of inheritance for gene: C19orf12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Marked gene: ATP1A3 as ready
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Gene: atp1a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Phenotypes for gene: ATP1A3 were changed from to ATP1A3-associated neurological disorder MONDO:0700002
Early-onset Parkinson disease v0.271 ATP1A3 Bryony Thompson Publications for gene: ATP1A3 were set to
Early-onset Parkinson disease v0.270 ATP1A3 Bryony Thompson Mode of inheritance for gene: ATP1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Classified gene: ATP1A3 as Green List (high evidence)
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a major feature of the condition
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Gene: atp1a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Marked gene: ATP13A2 as ready
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Gene: atp13a2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Phenotypes for gene: ATP13A2 were changed from to parkinsonism due to ATP13A2 deficiency MONDO:0017809
Early-onset Parkinson disease v0.267 ATP13A2 Bryony Thompson Publications for gene: ATP13A2 were set to
Early-onset Parkinson disease v0.266 ATP13A2 Bryony Thompson Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.275 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal dysplasia v0.271 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Marked gene: LFNG as ready
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Spondylocostal Dysostosis v0.10 LFNG Elena Savva Phenotypes for gene: LFNG were changed from Spondylocostal dysostosis 3, autosomal recessive MIM#609813 to Spondylocostal dysostosis 3, autosomal recessive MIM#609813
Spondylocostal Dysostosis v0.10 LFNG Elena Savva Phenotypes for gene: LFNG were changed from to Spondylocostal dysostosis 3, autosomal recessive MIM#609813
Spondylocostal Dysostosis v0.9 LFNG Elena Savva Marked gene: LFNG as ready
Spondylocostal Dysostosis v0.9 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Phenotypes for gene: LFNG were changed from to Spondylocostal dysostosis 3, autosomal recessive, MIM#609813
Skeletal Dysplasia_Fetal v0.216 LFNG Elena Savva Publications for gene: LFNG were set to
Skeletal Dysplasia_Fetal v0.216 LFNG Elena Savva Mode of inheritance for gene: LFNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.270 LFNG Elena Savva Marked gene: LFNG as ready
Skeletal dysplasia v0.270 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Skeletal dysplasia v0.270 LFNG Elena Savva Publications for gene: LFNG were set to 30196550; 16385447
Skeletal dysplasia v0.270 LFNG Elena Savva Phenotypes for gene: LFNG were changed from Spondylocostal dysostosis 3, autosomal recessive 609813 to Spondylocostal dysostosis 3, autosomal recessive MIM#609813
Skeletal dysplasia v0.269 LFNG Elena Savva Classified gene: LFNG as Green List (high evidence)
Skeletal dysplasia v0.269 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Polydactyly v0.274 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Polydactyly v0.274 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Polydactyly v0.273 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Polydactyly v0.273 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Polydactyly v0.272 RAB34 Elena Savva Marked gene: RAB34 as ready
Polydactyly v0.272 RAB34 Elena Savva Gene: rab34 has been classified as Red List (Low Evidence).
Polydactyly v0.272 RAB34 Elena Savva gene: RAB34 was added
gene: RAB34 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to 37619988; 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988
- Compound heterozygous variants identified in a fetus with multiple malformations, including a combination of rarely occurring pre- and postaxial polydactyly.
- Rab34-/- mice displayed polydactyly.

PMID: 37384395
- Biallelic variants in RAB34 were identified in 3 unrelated families. All affected individuals presented a novel form of OFDS accompanied by prexial and central polydactyly/bilateral polysyndactyly
Sources: Literature
Skeletal dysplasia v0.268 RAB34 Elena Savva Marked gene: RAB34 as ready
Skeletal dysplasia v0.268 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.268 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Skeletal dysplasia v0.268 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.267 RAB34 Elena Savva gene: RAB34 was added
gene: RAB34 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to 37619988; 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988
- Compound heterozygous variants identified in RAB34 in a fetus with multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly.
- Rab34-/- mice displayed a ciliopathy phenotype with cleft palate and polydactyly.

PMID: 37384395
- Biallelic variants in RAB34 were identified in 3 unrelated families. Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, and brain malformations), resulting in medical termination for three probands.
Sources: Literature
Skeletal Dysplasia_Fetal v0.215 KIAA0586 Elena Savva Publications for gene: KIAA0586 were set to
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Classified gene: KIAA0586 as Green List (high evidence)
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.214 KIAA0586 Elena Savva Phenotypes for gene: KIAA0586 were changed from to Joubert syndrome 23 MIM#616490; Short-rib thoracic dysplasia 14 with polydactyly MIM#616546
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Classified gene: KIAA0586 as Green List (high evidence)
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.214 KIAA0586 Elena Savva Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.265 KIAA0586 Elena Savva Marked gene: KIAA0586 as ready
Skeletal dysplasia v0.265 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.265 KIAA0586 Elena Savva gene: KIAA0586 was added
gene: KIAA0586 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0586 were set to PMID: 36538006; 26096313; 26166481
Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23 MIM#616490; Short-rib thoracic dysplasia 14 with polydactyly MIM#616546
Review for gene: KIAA0586 was set to GREEN
Added comment: PMID: 36538006 - fetus with post-axial polydactyly, short limbs and persistent left superior vena cava (PLSVC) with a dilated coronary sinus. Chet variants c.3940+1G>A
and c.3303G>A (synonymous) were identified. Functional studies support an impact for both variants.

PMID: 26096313 - 9 unrelated families with Joubert syndrome. MRI shows the molar tooth sign in 3/3 scanned patients. Patients tended to have biallelic PTCs, though missense also reported. p.Arg143Lysfs*4 appears to be a recurring mutation, seen in patients either as a homozygote or in chet with another unique mutation in 7/9 families. Interestingly these 7 families were of different ethnicity

PMID: 26166481 - Four unrelated families reported with a severe neurological/skeletal phenotype. However, note same variant identified in three of the families, indicative of founder effect. Gene is also associated with Joubert syndrome.
Sources: Literature
Skeletal dysplasia v0.264 HYLS1 Elena Savva Marked gene: HYLS1 as ready
Skeletal dysplasia v0.264 HYLS1 Elena Savva Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.264 HYLS1 Elena Savva Phenotypes for gene: HYLS1 were changed from to Hydrolethalus syndrome MIM#236680
Skeletal dysplasia v0.264 HYLS1 Elena Savva Publications for gene: HYLS1 were set to
Skeletal dysplasia v0.263 HYLS1 Elena Savva Classified gene: HYLS1 as Amber List (moderate evidence)
Skeletal dysplasia v0.263 HYLS1 Elena Savva Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Skeletal Dysplasia_Fetal v0.213 HYLS1 Elena Savva Publications for gene: HYLS1 were set to 15843405; 18648327; 19400947; 19656802; 32509774; 26830932
Skeletal Dysplasia_Fetal v0.212 HYLS1 Elena Savva edited their review of gene: HYLS1: Added comment: PMID: 34212369 - additional two fetuses with a phenotype of HLS with brain abnormalities, limbs malformations with pre and postaxial hexadactyly and abnormal genitalia. Probands were het for the Finnish founder variant (p.Asp211Gly) but each chet with a novel variant (p.(Arg221Pro, p.(Arg205*)). One fetus had occipital meningocele
molar tooth sign, the other craniorachischisis; Changed publications: PMID: 26830932, 34212369, 15843405, 18648327, 19400947, 19656802, 32509774; Changed phenotypes: Hydrolethalus syndrome MIM#236680
Prepair 1000+ v1.4 PIEZO1 Crystle Lee gene: PIEZO1 was added
gene: PIEZO1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: PIEZO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO1 were set to PMID: 26333996
Phenotypes for gene: PIEZO1 were set to Lymphatic malformation 6, MIM#616843
Review for gene: PIEZO1 was set to GREEN
Added comment: Biallelic mutations in PIEZO1 reported in 10 patients from 6 families with generalized lymphatic dysplasia (GLD) This is characterized by a uniform, widespread lymphedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions.
Sources: Literature
Mendeliome v1.1546 ANKZF1 Zornitza Stark reviewed gene: ANKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302725, 36857589; Phenotypes: Infantile-onset inflammatory bowel disease, MONDO:0005265, ANKZF1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.118 ANKZF1 Zornitza Stark Publications for gene: ANKZF1 were set to 28302725
Inflammatory bowel disease v0.117 ANKZF1 Zornitza Stark Mode of inheritance for gene: ANKZF1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.116 ANKZF1 Zornitza Stark Classified gene: ANKZF1 as Green List (high evidence)
Inflammatory bowel disease v0.116 ANKZF1 Zornitza Stark Gene: ankzf1 has been classified as Green List (High Evidence).
Mendeliome v1.1546 CARD8 Zornitza Stark Classified gene: CARD8 as Amber List (moderate evidence)
Mendeliome v1.1546 CARD8 Zornitza Stark Gene: card8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1545 CARD8 Zornitza Stark edited their review of gene: CARD8: Added comment: Additional individual reported with JRA and IBD.; Changed rating: AMBER; Changed publications: 29408806, 37724393
Inflammatory bowel disease v0.115 CARD8 Zornitza Stark Classified gene: CARD8 as Amber List (moderate evidence)
Inflammatory bowel disease v0.115 CARD8 Zornitza Stark Gene: card8 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Marked gene: HSPA1L as ready
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Classified gene: HSPA1L as Amber List (moderate evidence)
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.192 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Clefting disorders v0.250 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Callosome v0.516 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.12 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Orofaciodigital syndrome 20, MIM#620718 to Orofaciodigital syndrome 20, MIM#620718
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.11 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Radial Ray Abnormalities v1.10 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Mendeliome v1.1545 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Ciliopathies v1.49 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.212 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.211 RAB34 Zornitza Stark reviewed gene: RAB34: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome 20, MIM#620718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1544 ONECUT1 Bryony Thompson Marked gene: ONECUT1 as ready
Mendeliome v1.1544 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Mendeliome v1.1544 ONECUT1 Bryony Thompson Classified gene: ONECUT1 as Green List (high evidence)
Mendeliome v1.1544 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Mendeliome v1.1543 ONECUT1 Bryony Thompson gene: ONECUT1 was added
gene: ONECUT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ONECUT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ONECUT1 were set to 37639628; 34663987; 10825208
Phenotypes for gene: ONECUT1 were set to Neonatal diabetes mellitus MONDO:0016391
Review for gene: ONECUT1 was set to GREEN
Added comment: 3 unrelated neonatal diabetes cases with homozygous variants & supporting iPSC/mouse models
PMID: 37639628 - UK biobank study of ONECUT1 variants in neonatal diabetes mellitus (NDM), MODY, and type 2 diabetes. Identified a case with syndromic NDM with a homozygous frameshift (p.Met289Argfs*8). Rare heterozygous variants were not enriched in individuals with suspected MODY (n=484). Heterozygous null variants were significantly associated with type 2 diabetes (p=0.006) as a potential susceptibility gene.

PMID: 34663987 - 2 consanguineous families with homozygous variants (Glu231Ter or Glu231Asp) in cases with syndromic ND. Directed differentiation of human pluripotent stem cells revealed that loss of ONECUT1 impairs pancreatic progenitor formation.

PMID: 10825208 - Hnf6 (old gene name) null mice have diabetes
Sources: Literature
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Marked gene: ONECUT1 as ready
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Phenotypes for gene: ONECUT1 were changed from Syndromic diabetes to Syndromic diabetes; Neonatal diabetes mellitus MONDO:0016391
Monogenic Diabetes v0.45 ONECUT1 Bryony Thompson Publications for gene: ONECUT1 were set to PMID: 34663987
Monogenic Diabetes v0.44 ONECUT1 Bryony Thompson Classified gene: ONECUT1 as Green List (high evidence)
Monogenic Diabetes v0.44 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.43 ONECUT1 Bryony Thompson reviewed gene: ONECUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37639628, 34663987, 10825208; Phenotypes: Neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.113 HSPA1L Zornitza Stark gene: HSPA1L was added
gene: HSPA1L was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPA1L were set to 28126021
Phenotypes for gene: HSPA1L were set to inflammatory bowel disease, MONDO:0005265, HSPA1L-related
Review for gene: HSPA1L was set to AMBER
Added comment: PMID:28126021 reported the identification of a heterozygous de novo variant (p.Ser277Leu) in HSPA1L in a patient with inflammatory bowel disease. In addition, five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) were identified in six patients from a cohort of 136 IBD patients with WES data. Functional studies showed that all six HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity.

However, the variants identified are present at relatively high frequencies in gnomad V4, in particular p.Thr267Ile is present in 281 individuals, and the p.Ala268Thr is present in 4,753 individuals.
Sources: Literature
Mendeliome v1.1542 HSPA1L Zornitza Stark Marked gene: HSPA1L as ready
Mendeliome v1.1542 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1542 HSPA1L Zornitza Stark Classified gene: HSPA1L as Amber List (moderate evidence)
Mendeliome v1.1542 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1541 HSPA1L Zornitza Stark reviewed gene: HSPA1L: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v1.34 SCGN Zornitza Stark Marked gene: SCGN as ready
Autoinflammatory Disorders v1.34 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.34 SCGN Zornitza Stark Classified gene: SCGN as Amber List (moderate evidence)
Autoinflammatory Disorders v1.34 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.33 SCGN Zornitza Stark gene: SCGN was added
gene: SCGN was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SCGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCGN were set to 31663849
Phenotypes for gene: SCGN were set to ulcerative colitis, MONDO:0005101
Review for gene: SCGN was set to AMBER
Added comment: PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis.
Sources: Literature
Mendeliome v1.1541 SCGN Zornitza Stark Marked gene: SCGN as ready
Mendeliome v1.1541 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1541 SCGN Zornitza Stark Classified gene: SCGN as Amber List (moderate evidence)
Mendeliome v1.1541 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v1.32 SIRT1 Zornitza Stark Marked gene: SIRT1 as ready
Autoinflammatory Disorders v1.32 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Autoinflammatory Disorders v1.32 SIRT1 Zornitza Stark gene: SIRT1 was added
gene: SIRT1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIRT1 were set to 23473037
Phenotypes for gene: SIRT1 were set to autoimmune disease, MONDO:0007179, SIRT1-related
Review for gene: SIRT1 was set to RED
Added comment: PMID:23473037 reported the identification of a missense SIRT1 variant (p.Leu107Pro) in five members of a single family and all five of them had autoimmune disorder, four had type I diabetes and one had ulcerative colitis.
Sources: Literature
Mendeliome v1.1540 SIRT1 Zornitza Stark Marked gene: SIRT1 as ready
Mendeliome v1.1540 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Mendeliome v1.1540 SIRT1 Zornitza Stark Classified gene: SIRT1 as Red List (low evidence)
Mendeliome v1.1540 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Marked gene: TNRC6A as ready
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Gene: tnrc6a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Phenotypes for gene: TNRC6A were changed from ?Epilepsy, familial adult myoclonic, 6 MIM#618074 to Epilepsy, familial adult myoclonic, 6 MIM#618074
Mendeliome v1.1539 TNRC6A Elena Savva Marked gene: TNRC6A as ready
Mendeliome v1.1539 TNRC6A Elena Savva Gene: tnrc6a has been classified as Red List (Low Evidence).
Mendeliome v1.1539 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2289 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2289 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2288 TLK2 Elena Savva Marked gene: TLK2 as ready
Genetic Epilepsy v0.2288 TLK2 Elena Savva Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2288 TLK2 Elena Savva Classified gene: TLK2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2288 TLK2 Elena Savva Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2287 TLK2 Elena Savva gene: TLK2 was added
gene: TLK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TLK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TLK2 were set to 37662408; 31558842
Phenotypes for gene: TLK2 were set to Intellectual developmental disorder, autosomal dominant 57 MIM#618050
Review for gene: TLK2 was set to AMBER
Added comment: Seizures (13%) in OMIM

PMID: 37662408 - NOT PEER REVIEWED. Patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency. De novo missense found, but also another de novo PTC in MDM1. Functional studies support missense pathogenicity

PMID: 31558842 - HOM missense patient with a severe neurodev disorder, parents are clinically unaffected. She presented with epileptic spasms at the age of 6 months. Her EEG showed hypsarrhythmia suggesting West syndrome. She has been seizure-free since 3 years of age.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5698 FBXO31 Lucy Spencer reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1538 FBXO31 Lucy Spencer reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1538 SIRT1 Achchuthan Shanmugasundram gene: SIRT1 was added
gene: SIRT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIRT1 were set to 23473037
Phenotypes for gene: SIRT1 were set to autoimmune disease, MONDO:0007179
Review for gene: SIRT1 was set to RED
Added comment: PMID:23473037 reported the identification of a missense SIRT1 variant (p.Leu107Pro) in five members of a single family and all five of them had autoimmune disorder, four had type I diabetes and one had ulcerative colitis.
Sources: Literature
Mendeliome v1.1538 SCGN Achchuthan Shanmugasundram gene: SCGN was added
gene: SCGN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCGN were set to 31663849
Phenotypes for gene: SCGN were set to ulcerative colitis, MONDO:0005101
Review for gene: SCGN was set to AMBER
Added comment: PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis.
Sources: Literature
Mendeliome v1.1538 HSPA1L Achchuthan Shanmugasundram gene: HSPA1L was added
gene: HSPA1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPA1L were set to 28126021
Phenotypes for gene: HSPA1L were set to inflammatory bowel disease, MONDO:0005265
Review for gene: HSPA1L was set to GREEN
Added comment: PMID:28126021 reported the identification of a heterozygous de novo variant (p.Ser277Leu) in HSPA1L in a patient with inflammatory bowel disease. In addition, five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) were identified in six patients from a cohort of 136 IBD patients with WES data.

Functional studies showed that all six HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity.
Sources: Literature
Inflammatory bowel disease v0.112 CARD8 Achchuthan Shanmugasundram reviewed gene: CARD8: Rating: AMBER; Mode of pathogenicity: None; Publications: 37724393; Phenotypes: ?Inflammatory bowel disease (Crohn disease) 30, OMIM:619079; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.112 ANKZF1 Achchuthan Shanmugasundram reviewed gene: ANKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302725, 36857589; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegeneration with brain iron accumulation v0.31 DDHD1 Shekeeb Mohammad gene: DDHD1 was added
gene: DDHD1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: DDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDHD1 were set to 28818478
Phenotypes for gene: DDHD1 were set to spastic paraplegia; sensory neuropathy
Review for gene: DDHD1 was set to GREEN
gene: DDHD1 was marked as current diagnostic
Added comment: Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 THAP1 Shekeeb Mohammad gene: THAP1 was added
gene: THAP1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: THAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THAP1 were set to 38094642; 33665847
Phenotypes for gene: THAP1 were set to cervical dystonia; dystonia; dystonic tremor
Review for gene: THAP1 was set to GREEN
gene: THAP1 was marked as current diagnostic
Added comment: 3 published cases; 1 under clinical care with a pathogenic THAP1 variant.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 SQSTM1 Shekeeb Mohammad gene: SQSTM1 was added
gene: SQSTM1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SQSTM1 were set to 27545679
Phenotypes for gene: SQSTM1 were set to ataxia; dystonia; gaze palsy; neuroregression; cognitive decline; childhood dementia
Review for gene: SQSTM1 was set to GREEN
gene: SQSTM1 was marked as current diagnostic
Added comment: Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 ATP7B Shekeeb Mohammad reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33680437, 28376267, 34289020; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Marked gene: FLNA as ready
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to Heterotopia, periventricular, 1, MIM# 300049
Genetic Epilepsy v0.2285 FLNA Zornitza Stark Publications for gene: FLNA were set to
Genetic Epilepsy v0.2284 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Marked gene: FKTN as ready
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Gene: fktn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from to Muscular dystrophy-dystroglycanopathy MONDO:0018276
Genetic Epilepsy v0.2282 FKTN Zornitza Stark Publications for gene: FKTN were set to
Genetic Epilepsy v0.2281 FKTN Zornitza Stark Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2280 FKTN Zornitza Stark reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Marked gene: FBXL4 as ready
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Gene: fbxl4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Phenotypes for gene: FBXL4 were changed from to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471
Genetic Epilepsy v0.2279 FBXL4 Zornitza Stark Publications for gene: FBXL4 were set to
Genetic Epilepsy v0.2278 FBXL4 Zornitza Stark Mode of inheritance for gene: FBXL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2277 FBXL4 Zornitza Stark reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Marked gene: FARS2 as ready
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Gene: fars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Phenotypes for gene: FARS2 were changed from to combined oxidative phosphorylation defect type 14 MONDO:0013986
Genetic Epilepsy v0.2276 FARS2 Zornitza Stark Publications for gene: FARS2 were set to
Genetic Epilepsy v0.2275 FARS2 Zornitza Stark Mode of inheritance for gene: FARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Marked gene: TET3 as ready
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Gene: tet3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Classified gene: TET3 as Green List (high evidence)
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Gene: tet3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2273 TET3 Zornitza Stark reviewed gene: TET3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Beck-Fahrner syndrome MIM#618798; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.191 THOC2 Zornitza Stark Phenotypes for gene: THOC2 were changed from Mental retardation, X-linked 12/35 MIM#300957 to Mental retardation, X-linked 12/35 MIM#300957; Arthrogryposis (MONDO:0008779), THOC2-related
Fetal anomalies v1.190 THOC2 Zornitza Stark Publications for gene: THOC2 were set to 26166480; 32116545; 29851191; 32960281
Fetal anomalies v1.189 THOC2 Zornitza Stark edited their review of gene: THOC2: Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal. Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype

PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle; Changed publications: 29851191, 34976470, 37945483; Changed phenotypes: Mental retardation, X-linked 12/35 MIM#300957, Arthrogryposis (MONDO:0008779), THOC2-related
Genetic Epilepsy v0.2273 TK2 Elena Savva Marked gene: TK2 as ready
Genetic Epilepsy v0.2273 TK2 Elena Savva Gene: tk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2273 TK2 Elena Savva Classified gene: TK2 as Green List (high evidence)
Genetic Epilepsy v0.2273 TK2 Elena Savva Gene: tk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2272 TK2 Elena Savva gene: TK2 was added
gene: TK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TK2 were set to 25446393; 16504786
Phenotypes for gene: TK2 were set to Mitochondrial DNA depletion syndrome 2 (myopathic type), MIM#609560; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3, MIM# 617069
Review for gene: TK2 was set to GREEN
Added comment: GeneReviews: Seizures 11/34 (32%) in infantile onset cases

PMID: 25446393 - two siblings with chet missense, presenting with early onset myopathy with profound loss of muscle mass, axonal neuropathy, respiratory failure as well as severe brain atrophy with status epilepticus.

PMID: 16504786 - five children in two families reported with infantile encephalomyopathy with biallelic missense. Generalised seizures described in 2/3 siblings from one family
Sources: Literature
Genetic Epilepsy v0.2271 THOC2 Elena Savva Marked gene: THOC2 as ready
Genetic Epilepsy v0.2271 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2271 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2271 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2270 THOC2 Elena Savva gene: THOC2 was added
gene: THOC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: THOC2 were set to PMID: 26166480; 29851191
Phenotypes for gene: THOC2 were set to Intellectual developmental disorder, X-linked 12 MIM#300957
Review for gene: THOC2 was set to AMBER
Added comment: Seizures (in some patients) described in OMIM

PMID: 26166480 - gene-disease establishing paper, epilepsy described in 5/20 individuals where affected individuals were from three families. Only missense reported but all segregated well in families and had backing functional studies.

PMID: 29851191 - overlapping authors with ^, expanded cohort. Only 1/7 probands had epilepsy with an additional proband "suspected"
Sources: Literature
Arthrogryposis v0.405 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.405 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.405 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.405 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.404 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.404 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.403 THOC2 Elena Savva Marked gene: THOC2 as ready
Arthrogryposis v0.403 THOC2 Elena Savva Gene: thoc2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.403 THOC2 Elena Savva gene: THOC2 was added
gene: THOC2 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: THOC2 were set to PMID: 34976470; 37945483
Phenotypes for gene: THOC2 were set to Arthrogryposis (MONDO:0008779), THOC2-related
Review for gene: THOC2 was set to AMBER
Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal.
Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype

PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle
Sources: Literature
Genetic Epilepsy v0.2269 TGIF1 Elena Savva Marked gene: TGIF1 as ready
Genetic Epilepsy v0.2269 TGIF1 Elena Savva Gene: tgif1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2269 TGIF1 Elena Savva gene: TGIF1 was added
gene: TGIF1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TGIF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TGIF1 were set to Holoprosencephaly 4 MIM#142946
Review for gene: TGIF1 was set to RED
Added comment: Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2268 TET3 Elena Savva gene: TET3 was added
gene: TET3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TET3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TET3 were set to 36192301
Phenotypes for gene: TET3 were set to Beck-Fahrner syndrome MIM#618798
Review for gene: TET3 was set to AMBER
Added comment: Seizures (in some patients) noted in OMIM

GeneReviews: seizure disorder described in 9/24 patients

PMID: 36192301 - de novo PTC, generalized tonic-clonic seizures began at 5yo

Difficulty finding additional literature stating patient phenotypes
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5698 TET3 Elena Savva Phenotypes for gene: TET3 were changed from Intellectual disability; dysmorphic features; abnormal growth; movement disorders to Beck-Fahrner syndrome MIM#618798
Mendeliome v1.1538 TET3 Elena Savva Phenotypes for gene: TET3 were changed from Intellectual disability; dysmorphic features; abnormal growth; movement disorders to Beck-Fahrner syndrome MIM#618798
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva Marked gene: TBC1D7 as ready
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva Gene: tbc1d7 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva gene: TBC1D7 was added
gene: TBC1D7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TBC1D7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D7 were set to 23687350; 24515783
Phenotypes for gene: TBC1D7 were set to Macrocephaly/megalencephaly syndrome, autosomal recessive MIM#248000
Review for gene: TBC1D7 was set to RED
Added comment: PMID: 23687350 - There is no history of seizures in two siblings, but EEG recording showed some epileptic activity in the right temporal lobe

PMID: 24515783 - There is no history of seizures; EEG and brain SPECT were normal.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Marked gene: EIF2B4 as ready
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Added comment: Comment when marking as ready: Seizures are a feature.
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Gene: eif2b4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Phenotypes for gene: EIF2B4 were changed from to leukoencephalopathy with vanishing white matter MONDO:0011380
Genetic Epilepsy v0.2265 EIF2B4 Zornitza Stark Publications for gene: EIF2B4 were set to
Genetic Epilepsy v0.2264 EIF2B4 Zornitza Stark Mode of inheritance for gene: EIF2B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Marked gene: EIF2B3 as ready
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Gene: eif2b3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Phenotypes for gene: EIF2B3 were changed from to leukoencephalopathy with vanishing white matter MONDO:0011380
Genetic Epilepsy v0.2262 EIF2B3 Zornitza Stark Publications for gene: EIF2B3 were set to
Genetic Epilepsy v0.2261 EIF2B3 Zornitza Stark Mode of inheritance for gene: EIF2B3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Marked gene: EIF2B2 as ready
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Gene: eif2b2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Phenotypes for gene: EIF2B2 were changed from to Leukoencephalopathy with vanishing white matter, MIM#603896; Ovarioleukodystrophy, MIM# 603896
Genetic Epilepsy v0.2259 EIF2B2 Zornitza Stark Publications for gene: EIF2B2 were set to
Genetic Epilepsy v0.2258 EIF2B2 Zornitza Stark Mode of inheritance for gene: EIF2B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Phenotypes for gene: EIF2B1 were changed from to Leukoencephalopathy with vanishing white matter MIM#603896; Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Genetic Epilepsy v0.2256 EIF2B1 Zornitza Stark Publications for gene: EIF2B1 were set to
Genetic Epilepsy v0.2255 EIF2B1 Zornitza Stark Mode of inheritance for gene: EIF2B1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2254 POMK Zornitza Stark Marked gene: POMK as ready
Genetic Epilepsy v0.2254 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2254 POMK Zornitza Stark Classified gene: POMK as Amber List (moderate evidence)
Genetic Epilepsy v0.2254 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2253 POMK Zornitza Stark reviewed gene: POMK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 MIM#615249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1537 PRDM8 Zornitza Stark Marked gene: PRDM8 as ready
Mendeliome v1.1537 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Mendeliome v1.1537 PRDM8 Zornitza Stark gene: PRDM8 was added
gene: PRDM8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PRDM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM8 were set to 2296154; 35034233
Phenotypes for gene: PRDM8 were set to Epilepsy, progressive myoclonic, 10 MIM#616640
Review for gene: PRDM8 was set to RED
Added comment: - PMID:22961547, 3 individuals from one family, all with myoclonic epilepsy, all had the Phe261Leu variant. This variant is absent from gnomAD V4.
- PMID: 35034233, Two individuals from one family, no clinical seizures but presented with myoclonus and abnormal EEG (generalised epileptiform charges), these individuals had the Ala230Gly missense change, which has currently been reported as a VUS.
Sources: Expert list
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Marked gene: PRDM8 as ready
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Classified gene: PRDM8 as Red List (low evidence)
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2252 PRDM8 Zornitza Stark Classified gene: PRDM8 as Red List (low evidence)
Genetic Epilepsy v0.2252 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Mendeliome v1.1536 PRIMA1 Zornitza Stark Marked gene: PRIMA1 as ready
Mendeliome v1.1536 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Mendeliome v1.1536 PRIMA1 Zornitza Stark gene: PRIMA1 was added
gene: PRIMA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PRIMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIMA1 were set to 26339676
Phenotypes for gene: PRIMA1 were set to Frontal Lobe Epilepsy MONDO:0002612
Review for gene: PRIMA1 was set to RED
Added comment: - 2/3 siblings from unaffected parents in PMID: 26339676 were diagnosed with nocturnal frontal lobe epilepsy, which was confirmed by EEG. The affected siblings were homozygous for the c.93+2T>C variant canonical splice site variant. This variant was demonstrated by mini-gene assay to skip exon 2 of PRIMA1. Overall 1 family, 2 individuals with epilepsy and high impact variants in PRIMA1.
Sources: Expert list
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Marked gene: PRIMA1 as ready
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Classified gene: PRIMA1 as Red List (low evidence)
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Fetal anomalies v1.189 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Fetal anomalies v1.188 MAX Zornitza Stark reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5697 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Polydactyly v0.271 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Polydactyly v0.270 MAX Zornitza Stark reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1535 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300; Syndromic disease (MONDO:0002254), MAX-related to {Pheochromocytoma, susceptibility to}, MIM# 171300; Polydactyly-macrocephaly syndrome, MIM# 620712
Macrocephaly_Megalencephaly v0.139 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark reviewed gene: MAX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Publications for gene: PPP2R5D were set to
Genetic Epilepsy v0.2249 PPP2R5D Zornitza Stark Classified gene: PPP2R5D as Green List (high evidence)
Genetic Epilepsy v0.2249 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Classified gene: POMGNT2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2247 POMGNT2 Zornitza Stark reviewed gene: POMGNT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8 MIM#614830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Marked gene: POGZ as ready
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Classified gene: POGZ as Green List (high evidence)
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Mendeliome v1.1534 PLXNC1 Zornitza Stark Marked gene: PLXNC1 as ready
Mendeliome v1.1534 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Mendeliome v1.1534 PLXNC1 Zornitza Stark gene: PLXNC1 was added
gene: PLXNC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLXNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXNC1 were set to 36808730
Phenotypes for gene: PLXNC1 were set to Malformations of cortical development
Review for gene: PLXNC1 was set to RED
Added comment: This gene was included in the genes4epilepsy resource (PMID:36808730) and was reported as being associated with the clinical phenotype "malformations of cortical development". There are no current PubMed articles linking this gene with epilepsy however
Sources: Expert list
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Marked gene: PLXNC1 as ready
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Classified gene: PLXNC1 as Red List (low evidence)
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Marked gene: PEX13 as ready
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Classified gene: PEX13 as Green List (high evidence)
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Marked gene: PEX10 as ready
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Gene: pex10 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Classified gene: PEX10 as Red List (low evidence)
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Gene: pex10 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Marked gene: PCLO as ready
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Classified gene: PCLO as Red List (low evidence)
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Gene: pax6 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Classified gene: PAX6 as Amber List (moderate evidence)
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Gene: pax6 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Marked gene: PAK3 as ready
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Gene: pak3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Classified gene: PAK3 as Amber List (moderate evidence)
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Gene: pak3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Classified gene: OFD1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Marked gene: NR2F1 as ready
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Classified gene: NR2F1 as Green List (high evidence)
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Marked gene: NF1 as ready
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Gene: nf1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Classified gene: NF1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Gene: nf1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Marked gene: MCM3AP as ready
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Classified gene: MCM3AP as Red List (low evidence)
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Classified gene: LRPPRC as Amber List (moderate evidence)
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Classified gene: COL3A1 as Green List (high evidence)
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Marked gene: CHD1 as ready
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Gene: chd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Classified gene: CHD1 as Green List (high evidence)
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Gene: chd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2233 SERAC1 Zornitza Stark Classified gene: SERAC1 as Green List (high evidence)
Genetic Epilepsy v0.2233 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Mendeliome v1.1533 CASZ1 Zornitza Stark Marked gene: CASZ1 as ready
Mendeliome v1.1533 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Mendeliome v1.1533 CASZ1 Zornitza Stark Classified gene: CASZ1 as Green List (high evidence)
Mendeliome v1.1533 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Mendeliome v1.1532 CASZ1 Zornitza Stark gene: CASZ1 was added
gene: CASZ1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASZ1 were set to 28099117; 36293425; 31268246
Phenotypes for gene: CASZ1 were set to Dilated cardiomyopathy, MONDO:0005021, CASZ1-related; left ventricular non compaction
Review for gene: CASZ1 was set to GREEN
Added comment: Rare cause of paeditric onsent DCM. at least 3 papers report LoF variants, 2 of which each report a novel de novo frameshift variant in children diagnosed with DCM less than 1 and who died at 11 mths ( PMID: 31268246; Guo 2019) and 22mths (PMID: 36293425, Orlova 2022). Another paper (PMID: 28099117, Qiu 2017) reported a nonsense variant that segregated with DCM in a family in an AD fashion (full text not available).
Sources: Expert list
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Marked gene: CASZ1 as ready
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Phenotypes for gene: CASZ1 were changed from dilated cardiomyopathy, left ventricular non compaction to Dilated cardiomyopathy, MONDO:0005021, CASZ1-related; left ventricular non compaction
Cardiomyopathy_Paediatric v0.179 CASZ1 Zornitza Stark Classified gene: CASZ1 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.179 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2232 SRCAP Zornitza Stark Classified gene: SRCAP as Green List (high evidence)
Genetic Epilepsy v0.2232 SRCAP Zornitza Stark Gene: srcap has been classified as Green List (High Evidence).
Mendeliome v1.1531 SMC3 Zornitza Stark Publications for gene: SMC3 were set to 18996922; 25655089; 31334757
Genetic Epilepsy v0.2231 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743 to Neurodevelopmental disorder, MONDO:0700092
Genetic Epilepsy v0.2230 SYNE1 Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5696 TAF1C Zornitza Stark Marked gene: TAF1C as ready
Intellectual disability syndromic and non-syndromic v0.5696 TAF1C Zornitza Stark Gene: taf1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2229 TAOK1 Zornitza Stark Marked gene: TAOK1 as ready
Genetic Epilepsy v0.2229 TAOK1 Zornitza Stark Gene: taok1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5696 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to 22200994
Intellectual disability syndromic and non-syndromic v0.5695 NDUFB9 Zornitza Stark edited their review of gene: NDUFB9: Added comment: PMID: 38129218: Thr144Met, listed as ACMG-P, hom in 1x pt with mito complex I deficiency and leukodystrophy, no functional studies, both parents are het. However, this variant has 2 homozygotes in gnomADv4, so unlikely pathogenic.; Changed publications: 22200994, 38129218
Mitochondrial disease v0.916 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to
Mendeliome v1.1530 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to 22200994
Mendeliome v1.1529 NDUFB9 Zornitza Stark edited their review of gene: NDUFB9: Added comment: PMID: 38129218: Thr144Met, listed as ACMG-P, hom in 1x pt with mito complex I deficiency and leukodystrophy, no functional studies, both parents are het.

However, this variant has 2 homozygotes in gnomADv4 so unlikely pathogenic.; Changed publications: 22200994, 38129218
Mitochondrial disease v0.915 NDUFB9 Chern Lim reviewed gene: NDUFB9: Rating: AMBER; Mode of pathogenicity: None; Publications: 38129218; Phenotypes: Mitochondrial complex I deficiency, nuclear type 24, MIM#618245; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal Macrocystic Disease v0.68 NEK8 Elena Savva Classified gene: NEK8 as Green List (high evidence)
Renal Macrocystic Disease v0.68 NEK8 Elena Savva Gene: nek8 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.67 NEK8 Elena Savva Publications for gene: NEK8 were set to Unpublished ESHG presentation
Mendeliome v1.1529 DNM2 Bryony Thompson reviewed gene: DNM2: Rating: RED; Mode of pathogenicity: None; Publications: 23092955; Phenotypes: fetal akinesia-cerebral and retinal hemorrhage syndrome MONDO:0014149; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Marked gene: NALCN as ready
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Classified gene: NALCN as Green List (high evidence)
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.66 NEK8 Lauren Rogers reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 37598857; Phenotypes: Familial cystic renal disease MONDO:0019741; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2228 TAOK1 Elena Savva gene: TAOK1 was added
gene: TAOK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAOK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TAOK1 were set to Developmental delay with or without intellectual impairment or behavioral abnormalities MIM#619575
Review for gene: TAOK1 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2228 TAOK1 Elena Savva gene: TAOK1 was added
gene: TAOK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAOK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TAOK1 were set to Developmental delay with or without intellectual impairment or behavioral abnormalities MIM#619575
Review for gene: TAOK1 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2227 TANC2 Elena Savva Marked gene: TANC2 as ready
Genetic Epilepsy v0.2227 TANC2 Elena Savva Gene: tanc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2227 TANC2 Elena Savva Classified gene: TANC2 as Green List (high evidence)
Genetic Epilepsy v0.2227 TANC2 Elena Savva Gene: tanc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2226 TANC2 Elena Savva gene: TANC2 was added
gene: TANC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TANC2 were set to PMID: 31616000
Phenotypes for gene: TANC2 were set to Intellectual developmental disorder with autistic features and language delay, with or without seizures MIM#618906
Review for gene: TANC2 was set to GREEN
Added comment: PMID: 31616000 - 11/20 individuals had either a formal diagnosis of epilepsy (n = 9) or suffered from recurrent seizures (n = 2).
Sources: Literature
Genetic Epilepsy v0.2225 TAF1C Elena Savva Marked gene: TAF1C as ready
Intellectual disability syndromic and non-syndromic v0.5695 TAF1C Elena Savva Phenotypes for gene: TAF1C were changed from Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Genetic Epilepsy v0.2225 TAF1C Elena Savva Gene: taf1c has been classified as Red List (Low Evidence).
Mendeliome v1.1529 TAF1C Elena Savva Phenotypes for gene: TAF1C were changed from Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Genetic Epilepsy v0.2225 TAF1C Elena Savva gene: TAF1C was added
gene: TAF1C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAF1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF1C were set to 32779182
Phenotypes for gene: TAF1C were set to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Review for gene: TAF1C was set to RED
Added comment: Knuutinen et al (2020 - PMID: 32779182) report on 2 individuals from 2 consanguineous families, homozygous for TAF1C missense variants. Both presented with an early onset neurological phenotype with severe global DD, ID (2/2 - moderate and profound), spasticity (2/2), ophthalmic findings (strabismus 2/2, nystagmus 1/2). Epilepsy, abnormal brain MRI (cerebral and cerebellar atrophy and white matter hyperintensities) as well and additional findings were reported in one (always the same individual).

NO hom PTCs in gnomAD v4
Sources: Literature
Genetic Epilepsy v0.2224 SYNE1 Elena Savva Marked gene: SYNE1 as ready
Genetic Epilepsy v0.2224 SYNE1 Elena Savva Gene: syne1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2224 SYNE1 Elena Savva gene: SYNE1 was added
gene: SYNE1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SYNE1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SYNE1 were set to PMID: 31703138; 37096302; 30573412
Phenotypes for gene: SYNE1 were set to Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743
Review for gene: SYNE1 was set to RED
Added comment: PMID: 31703138 - PTC in a child featuring infantile epilepsy and developmental disorder, inherited from a father with a history of convulsions in infancy

PMID: 37096302;30573412 - review, no reports noted of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2223 SUMF1 Elena Savva Marked gene: SUMF1 as ready
Genetic Epilepsy v0.2223 SUMF1 Elena Savva Gene: sumf1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2223 SUMF1 Elena Savva gene: SUMF1 was added
gene: SUMF1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SUMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUMF1 were set to 36980153; 36959582
Phenotypes for gene: SUMF1 were set to Multiple sulfatase deficiency MIM#272200
Review for gene: SUMF1 was set to RED
Added comment: PMID: 36980153 - review, no patients described with seizures/epilepsy

PMID: 36959582 - review, no patients described with seizures/epilepsy. Single proband in the study reported to have intractable epilepsy during sleep EEG study

Gene was listed in the Oliver list
Sources: Literature
Mendeliome v1.1528 SMC3 Bryony Thompson reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38297832; Phenotypes: Cornelia de Lange syndrome MONDO:0016033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic Epilepsy v0.2222 SRCAP Elena Savva Classified gene: SRCAP as Amber List (moderate evidence)
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2222 SRCAP Elena Savva Marked gene: SRCAP as ready
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2222 SRCAP Elena Savva Classified gene: SRCAP as Amber List (moderate evidence)
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2221 SRCAP Elena Savva gene: SRCAP was added
gene: SRCAP was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SRCAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SRCAP were set to 23193612; 23621943
Phenotypes for gene: SRCAP were set to Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities MIM#619595; Floating-Harbor syndrome MIM#136140
Review for gene: SRCAP was set to AMBER
Added comment: OMIM: Seizures listed as a rare trait for both conditions

GeneReviews: Seizures have been observed in seven of 73 individuals.

PMID: 23621943: review, 6/52 patients reported with seizures
Sources: Literature
Genetic Epilepsy v0.2220 SOX11 Elena Savva Mode of pathogenicity for gene: SOX11 was changed from None to None
Genetic Epilepsy v0.2219 SOX11 Elena Savva Marked gene: SOX11 as ready
Genetic Epilepsy v0.2219 SOX11 Elena Savva Gene: sox11 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2219 SOX11 Elena Savva gene: SOX11 was added
gene: SOX11 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism MIM#615866
Review for gene: SOX11 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2218 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2218 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2217 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2217 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2217 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2217 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2216 SON Elena Savva Marked gene: SON as ready
Genetic Epilepsy v0.2216 SON Elena Savva Gene: son has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2216 SON Elena Savva gene: SON was added
gene: SON was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SON was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SON were set to PMID: 37488749; 27545680
Phenotypes for gene: SON were set to ZTTK syndrome MIM#617140
Review for gene: SON was set to GREEN
Added comment: Seizures (in some patients) noted in OMIM

PMID: 37488749 - review of 79 patients, seizures not described

PMID: 27545680 - 11 of 20 individuals developed seizures and/or epilepsy with an age of onset ranging from 1 to 6 years
Sources: Literature
Cardiomyopathy_Paediatric v0.178 CASZ1 Ivan Macciocca gene: CASZ1 was added
gene: CASZ1 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASZ1 were set to PMID: 28099117; 36293425; 31268246
Phenotypes for gene: CASZ1 were set to dilated cardiomyopathy, left ventricular non compaction
Penetrance for gene: CASZ1 were set to unknown
Review for gene: CASZ1 was set to GREEN
Added comment: rare cause of paeditric onsent DCM.
at least 3 papers report LoF variants, 2 of which each report a novel de novo frameshift variant in children diagnosed with DCM less than 1 and who died at 11 mths ( PMID: 31268246; Guo 2019) and 22mths (PMID: 36293425, Orlova 2022). Another paper (PMID: 28099117, Qiu 2017) reported a nonsense variant that segregated with DCM in a family in an AD fashion (full text not available).
Sources: Literature
Genetic Epilepsy v0.2215 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy MONDO:0020121 to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Genetic Epilepsy v0.2214 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Muscular dystrophy and myopathy_Paediatric v1.11 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy; Epilepsy to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Muscular dystrophy and myopathy_Paediatric v1.10 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Mendeliome v1.1528 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy, MONDO:0019950, BET1-related; Epilepsy to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Mendeliome v1.1527 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Intellectual disability syndromic and non-syndromic v0.5694 CSTF2 Zornitza Stark Phenotypes for gene: CSTF2 were changed from Intellectual disability to Intellectual developmental disorder, X-linked 113, MIM# 301116
Intellectual disability syndromic and non-syndromic v0.5693 CSTF2 Zornitza Stark edited their review of gene: CSTF2: Changed phenotypes: Intellectual developmental disorder, X-linked 113, MIM# 301116
Mendeliome v1.1527 CSTF2 Zornitza Stark Phenotypes for gene: CSTF2 were changed from Intellectual disability to Intellectual developmental disorder, X-linked 113, MIM# 301116
Mendeliome v1.1526 CSTF2 Zornitza Stark edited their review of gene: CSTF2: Changed phenotypes: Intellectual developmental disorder, X-linked 113, MIM# 301116
Hypertrophic cardiomyopathy_HCM v0.176 TTR Zornitza Stark Tag treatable tag was added to gene: TTR.
Mendeliome v1.1526 TTR Zornitza Stark Tag treatable tag was added to gene: TTR.
Fetal anomalies v1.188 NARS Zornitza Stark Marked gene: NARS as ready
Fetal anomalies v1.188 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Fetal anomalies v1.188 NARS Zornitza Stark Classified gene: NARS as Green List (high evidence)
Fetal anomalies v1.188 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.411 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert list
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.21 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Renal Ciliopathies and Nephronophthisis. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.122 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Fetal anomalies v1.187 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Fetal anomalies v1.187 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Fetal anomalies v1.187 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Fetal anomalies v1.187 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Fetal anomalies v1.186 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Mendeliome v1.1526 DLG5 Zornitza Stark Phenotypes for gene: DLG5 were changed from Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Yuksel-Vogel-Bauer syndrome, MIM#620703
Mendeliome v1.1525 DLG5 Zornitza Stark edited their review of gene: DLG5: Changed phenotypes: Yuksel-Vogel-Bauer syndrome, MIM#620703
Mendeliome v1.1525 DLG5 Zornitza Stark changed review comment from: Four unrelated families reported, supportive Xenopus animal model data.
Sources: Literature; to: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Literature
Ciliopathies v1.48 DLG5 Zornitza Stark Phenotypes for gene: DLG5 were changed from Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Yuksel-Vogel-Bauer syndrome, MIM#620703
Ciliopathies v1.47 DLG5 Zornitza Stark edited their review of gene: DLG5: Changed phenotypes: Yuksel-Vogel-Bauer syndrome, MIM#620703
Ciliopathies v1.47 DLG5 Zornitza Stark changed review comment from: Four unrelated families reported, supportive Xenopus animal model data.
Sources: Literature; to: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Marked gene: ASCC3 as ready
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Gene: ascc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Classified gene: ASCC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Gene: ascc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5692 ASCC3 Zornitza Stark gene: ASCC3 was added
gene: ASCC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: ASCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC3 were set to 21937992; 35047834
Phenotypes for gene: ASCC3 were set to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Review for gene: ASCC3 was set to GREEN
Added comment: Combined neuromuscular and neurobehavioral phenotype.

11 individuals from 7 unrelated families with homozygous (missense) or compound heterozygous variants (missense with a presumed LoF variant or 2 missense, no biallelic LoF) with a neurologic phenotype that ranges from severe developmental delay to muscle fatigue
Sources: Expert Review
Muscular dystrophy and myopathy_Paediatric v1.10 ASCC3 Zornitza Stark Phenotypes for gene: ASCC3 were changed from Congenital Myopathy (MONDO:0019952); Neuromuscular Symptoms to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Muscular dystrophy and myopathy_Paediatric v1.9 ASCC3 Zornitza Stark Publications for gene: ASCC3 were set to 35047834
Muscular dystrophy and myopathy_Paediatric v1.8 ASCC3 Zornitza Stark reviewed gene: ASCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35047834; Phenotypes: Intellectual developmental disorder, autosomal recessive 81, MIM# 620700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1525 ASCC3 Zornitza Stark Phenotypes for gene: ASCC3 were changed from Neuromuscular syndrome; congenital myopathy to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Mendeliome v1.1524 ASCC3 Zornitza Stark Publications for gene: ASCC3 were set to 21937992; https://doi.org/10.1016/j.xhgg.2021.100024
Mendeliome v1.1523 ASCC3 Zornitza Stark reviewed gene: ASCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 81, MIM# 620700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5691 GIGYF1 Zornitza Stark Phenotypes for gene: GIGYF1 were changed from Autism, Intellectual disability, GIGYF1-related (MONDO#0001071) to Autism spectrum disorder (MONDO:0005258), GIGYF1-related
Mendeliome v1.1523 GIGYF1 Zornitza Stark Phenotypes for gene: GIGYF1 were changed from Autism, Intellectual disability, GIGYF1-related (MONDO#0001071) to Autism spectrum disorder (MONDO:0005258), GIGYF1-related
Intellectual disability syndromic and non-syndromic v0.5690 SYN1 Zornitza Stark Mode of inheritance for gene: SYN1 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Marked gene: SNAP29 as ready
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Gene: snap29 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Classified gene: SNAP29 as Green List (high evidence)
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Gene: snap29 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2213 SNAP29 Elena Savva gene: SNAP29 was added
gene: SNAP29 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SNAP29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNAP29 were set to PMID: 33977139
Phenotypes for gene: SNAP29 were set to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome MIM#609528
Review for gene: SNAP29 was set to GREEN
Added comment: Seizures (in some patients) noted in OMIM

PMID: 33977139 - cohort of 6 probands, seizures detected in 3/6. Paper reviews previous reports, notes seizures in another cohort of 7/19
Sources: Literature
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva Marked gene: SMARCE1 as ready
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva Gene: smarce1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva gene: SMARCE1 was added
gene: SMARCE1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SMARCE1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMARCE1 were set to PMID: 30548424
Phenotypes for gene: SMARCE1 were set to Coffin-Siris syndrome 5 MIM#616938
Review for gene: SMARCE1 was set to RED
Added comment: PMID: 30548424 - Proband with a de novo splice variant (proven to result in inframe exon skipping), presented with seizures, hypotonia, GDD, ataxia etc.

No other literature showing SNVs in this gene and epilepsy/seizures. Gene was listed in the Oliver review
Sources: Literature
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Marked gene: SLC19A3 as ready
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Gene: slc19a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Classified gene: SLC19A3 as Green List (high evidence)
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Gene: slc19a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2210 SLC19A3 Elena Savva gene: SLC19A3 was added
gene: SLC19A3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC19A3 were set to PMID: 37670342; 23269594; 26863430
Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) MIM#607483
Review for gene: SLC19A3 was set to GREEN
Added comment: Seizures noted in OMIM

PMID: 37670342 - 1/21 probands had absence seizure on Depakene. Hom missense but many families in this paper had the same variant (likely founder).

PMID: 23269594 - 8/10 patients had acute-subacute onset consisting of ataxia, seizures, and encephalopathy. All probands had the same recurring missense described in PMID: 37670342.

PMID: 26863430 - two siblings with early-onset encephalopathy dystonia and epilepsy,
Sources: Literature
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Marked gene: SHANK3 as ready
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Classified gene: SHANK3 as Green List (high evidence)
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Classified gene: SHANK3 as Green List (high evidence)
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2208 SHANK3 Elena Savva gene: SHANK3 was added
gene: SHANK3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SHANK3 were set to PMID: 37655421
Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome MIM#606232
Review for gene: SHANK3 was set to GREEN
Added comment: Seizures listed in OMIM, SHANK3 is often involved in a 22q13.3 deletion

PMID: 37655421 - Proband with a PTC, presenting with epileptic seizures, impaired speech development

PMID: 36967043 - large review, considered patients who had the 22q13.3 deletion as well as SNVs. Prevalence of epilepsy ranged from 17-70% in one study, 27% in another study and 41% in another. Seizure type was highly variable, ranging from atypical absent, tonic, atonic, tonic-clonic and myoclonic.
Sources: Literature
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Marked gene: SERAC1 as ready
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Gene: serac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Classified gene: SERAC1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Gene: serac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2206 SERAC1 Elena Savva gene: SERAC1 was added
gene: SERAC1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERAC1 were set to PMID: 27186703; 24997715
Phenotypes for gene: SERAC1 were set to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome MIM#614739
Review for gene: SERAC1 was set to AMBER
Added comment: Seizures (less common) listed in OMIM

PMID: 27186703 - two sibling patients who presented with 3-methylglutaconic acid and 3-methylglutaric aciduria, microcephaly, growth retardation, dysmorphic features, severe sensorineural deafness, progressive spasticity, dystonia, seizures and basal ganglia involvement.

PMID: 24997715 - Proband with biallelic PTCs, presented with 3-methylglutaconic aciduria, sensorineural hearing loss, encephalopathy, and Leigh-like pattern on MRI, as well as developmental delay and developmental regression, bilateral optic nerve atrophy, microcephaly, and myoclonic epilepsy.

GeneReviews - 38% of patients have seizures (febrile, myoclonic)
Sources: Literature
Mendeliome v1.1522 HNRNPC Zornitza Stark Phenotypes for gene: HNRNPC were changed from Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related to Intellectual developmental disorder-74, MIM#620688
Mendeliome v1.1521 HNRNPC Zornitza Stark edited their review of gene: HNRNPC: Changed phenotypes: intellectual developmental disorder-74, MIM#620688
Intellectual disability syndromic and non-syndromic v0.5689 HNRNPC Zornitza Stark Phenotypes for gene: HNRNPC were changed from Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related to intellectual developmental disorder-74, MIM#620688
Intellectual disability syndromic and non-syndromic v0.5688 HNRNPC Zornitza Stark edited their review of gene: HNRNPC: Changed phenotypes: intellectual developmental disorder-74, MIM#620688
Genetic Epilepsy v0.2205 SCN10A Elena Savva Marked gene: SCN10A as ready
Genetic Epilepsy v0.2205 SCN10A Elena Savva Gene: scn10a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2205 SCN10A Elena Savva gene: SCN10A was added
gene: SCN10A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SCN10A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN10A were set to PMID: 28078312
Phenotypes for gene: SCN10A were set to Episodic pain syndrome, familial, 2 MIM#615551; Neurodevelopmental disorder (MONDO#0700092), SCN10A-related
Review for gene: SCN10A was set to RED
Added comment: PMID: 28078312 - three families (2x biallelic missense, hom PTC).
- family 1 had progressive neuromuscular disease, severe cognitive impairment, muscle weakness, upper motor neuron lesion, anhydrosis, facial dysmorphism, and recurrent seizures
- family 2 had neonatal hypotonia, bradycardia, and recurrent seizures
- family 3 had febrile infection-related epilepsy syndrome (FIRES)
- Additional 5 probands reported with biallelic missense and Lennox–Gastaut syndrome, epilepsy databases and autism databases
- Het carriers of PTC were NOT affected, but LOF is NOT a known mechanism of AD disease

Red for biallelic disease - none of the missense had functional studies to support pathogenicity. More evidence needed.
Sources: Literature
Genetic Epilepsy v0.2204 SACS Elena Savva Classified gene: SACS as Amber List (moderate evidence)
Genetic Epilepsy v0.2204 SACS Elena Savva Gene: sacs has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2203 SACS Elena Savva Classified gene: SACS as Amber List (moderate evidence)
Genetic Epilepsy v0.2203 SACS Elena Savva Gene: sacs has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2202 SACS Elena Savva Marked gene: SACS as ready
Genetic Epilepsy v0.2202 SACS Elena Savva Gene: sacs has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2202 SACS Elena Savva gene: SACS was added
gene: SACS was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SACS were set to PMID: 27871429; 35386405
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type MIM#270550
Review for gene: SACS was set to AMBER
Added comment: PMID: 27871429 - two consanguinous families (8 affecteds) with homozygous PTCs. Epilepsy observed for all 4/4 members of a single family. Authors note seizures may be present in 10% of SACS patients

PMID: 35386405 - Review of chinese patients, found 4/27 patients had epilepsy (one was questionable)
Sources: Literature
Genetic Epilepsy v0.2201 TMEM5 Elena Savva Marked gene: TMEM5 as ready
Genetic Epilepsy v0.2201 TMEM5 Elena Savva Gene: tmem5 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2201 TMEM5 Elena Savva gene: TMEM5 was added
gene: TMEM5 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TMEM5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM5 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 MIM#615041
Review for gene: TMEM5 was set to RED
Added comment: Alt, gene name RXYLT1

No literature showing SNVs in this gene and epilepsy/seizures. Gene was listed in the Oliver review
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Marked gene: WDR44 as ready
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Gene: wdr44 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Classified gene: WDR44 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Gene: wdr44 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5687 WDR44 Zornitza Stark gene: WDR44 was added
gene: WDR44 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1521 RIC1 Zornitza Stark Phenotypes for gene: RIC1 were changed from Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD to Cleft lip/palate MONDO:0016044, RIC1-related; Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD
Mendeliome v1.1520 RIC1 Zornitza Stark Publications for gene: RIC1 were set to 31932796
Mendeliome v1.1519 RIC1 Zornitza Stark Mode of inheritance for gene: RIC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1518 RIC1 Zornitza Stark Classified gene: RIC1 as Green List (high evidence)
Mendeliome v1.1518 RIC1 Zornitza Stark Gene: ric1 has been classified as Green List (High Evidence).
Fetal anomalies v1.185 MYMK Zornitza Stark Deleted their comment
Fetal anomalies v1.185 MYMK Zornitza Stark Classified gene: MYMK as Green List (high evidence)
Fetal anomalies v1.185 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Fetal anomalies v1.184 MYMK Zornitza Stark edited their review of gene: MYMK: Added comment: Cleft palate, micrognathia, microcephaly, talipes are features detectable on fetal ultrasound.; Changed rating: GREEN
Clefting disorders v0.249 MYMK Zornitza Stark Marked gene: MYMK as ready
Clefting disorders v0.249 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Clefting disorders v0.249 MYMK Zornitza Stark Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome 254940 to Carey-Fineman-Ziter syndrome, MIM# 254940
Clefting disorders v0.248 MYMK Zornitza Stark reviewed gene: MYMK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Carey-Fineman-Ziter syndrome, MIM# 254940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.248 FBXO11 Zornitza Stark Marked gene: FBXO11 as ready
Clefting disorders v0.248 FBXO11 Zornitza Stark Gene: fbxo11 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.248 FBXO11 Zornitza Stark reviewed gene: FBXO11: Rating: AMBER; Mode of pathogenicity: None; Publications: 30057029; Phenotypes: intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 618089; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.248 FOXP2 Zornitza Stark Marked gene: FOXP2 as ready
Clefting disorders v0.248 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Red List (Low Evidence).
Clefting disorders v0.248 FOXP2 Zornitza Stark Phenotypes for gene: FOXP2 were changed from Speech-language disorder-1, 602081 to Speech-language disorder-1, MIM# 602081
Clefting disorders v0.247 FOXP2 Zornitza Stark Classified gene: FOXP2 as Red List (low evidence)
Clefting disorders v0.247 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Red List (Low Evidence).
Clefting disorders v0.246 FOXP2 Zornitza Stark reviewed gene: FOXP2: Rating: RED; Mode of pathogenicity: None; Publications: 36328423; Phenotypes: Speech-language disorder-1, MIM# 602081; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Marked gene: ACACA as ready
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Classified gene: ACACA as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5685 ACACA Zornitza Stark gene: ACACA was added
gene: ACACA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACACA were set to 34552920; 10677481; 16717184; 36709796
Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency, MIM# 613933
Review for gene: ACACA was set to AMBER
Added comment: Two families with molecular testing, missense variants, supportive functional data.
Sources: Literature
Mendeliome v1.1517 ACACA Zornitza Stark Classified gene: ACACA as Amber List (moderate evidence)
Mendeliome v1.1517 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1516 ACACA Zornitza Stark reviewed gene: ACACA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36709796; Phenotypes: Acetyl-CoA carboxylase deficiency, MIM# 613933; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.38 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Moyamoya disease, MONDO:0016820, ANO1 related to Moyamoya disease 7, MIM# 620687
Cerebral vascular malformations v0.37 ANO1 Zornitza Stark reviewed gene: ANO1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Moyamoya disease 7, MIM# 620687; Mode of inheritance: None
Stroke v1.15 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from moyamoya; cerebral arteriopathy; stroke; MONDO:0016820 to Moyamoya disease 7, MIM# 620687
Stroke v1.14 ANO1 Zornitza Stark reviewed gene: ANO1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Moyamoya disease 7, MIM# 620687; Mode of inheritance: None
Mendeliome v1.1516 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Intestinal dysmotility syndrome, MIM# 620045; Moyamoya disease, MONDO:0016820, ANO1 related to Intestinal dysmotility syndrome, MIM# 620045; Moyamoya disease 7, MIM# 620687
Mendeliome v1.1515 ANO1 Zornitza Stark edited their review of gene: ANO1: Changed phenotypes: Intestinal dysmotility syndrome, MIM# 620045, Moyamoya disease 7, MIM# 620687
Proteinuria v0.222 NUP160 Zornitza Stark Classified gene: NUP160 as Green List (high evidence)
Proteinuria v0.222 NUP160 Zornitza Stark Gene: nup160 has been classified as Green List (High Evidence).
Proteinuria v0.221 NUP160 Zornitza Stark Deleted their comment
Proteinuria v0.221 NUP160 Zornitza Stark edited their review of gene: NUP160: Changed rating: GREEN
Proteinuria v0.221 NUP160 Zornitza Stark commented on gene: NUP160: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K).

Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.
Proteinuria v0.221 NUP160 Zornitza Stark edited their review of gene: NUP160: Added comment: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K).

Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.; Changed publications: 30910934, 30179222, 33456446, 38224683
Mendeliome v1.1515 NUP160 Zornitza Stark Publications for gene: NUP160 were set to 30179222
Mendeliome v1.1514 NUP160 Zornitza Stark Classified gene: NUP160 as Green List (high evidence)
Mendeliome v1.1514 NUP160 Zornitza Stark Gene: nup160 has been classified as Green List (High Evidence).
Mendeliome v1.1513 NUP160 Melanie Marty changed review comment from: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K). Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with steroid-resistant nephrotic syndrome and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse mode using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.; to: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K). Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.
Mendeliome v1.1513 NUP160 Melanie Marty reviewed gene: NUP160: Rating: GREEN; Mode of pathogenicity: None; Publications: 30910934, 30179222, 33456446, 38224683; Phenotypes: Steroid-resistant nephrotic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Marked gene: SP9 as ready
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5683 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: SP9 was set to GREEN
Added comment: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Sources: Literature
Mendeliome v1.1513 SP9 Zornitza Stark Marked gene: SP9 as ready
Mendeliome v1.1513 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Mendeliome v1.1513 SP9 Suliman Khan commented on gene: SP9: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Mendeliome v1.1513 SP9 Zornitza Stark Phenotypes for gene: SP9 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, SP9-related
Mendeliome v1.1512 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Mendeliome v1.1512 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Marked gene: WDR44 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well supported.
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Mendeliome v1.1511 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: SP9 was set to GREEN
Added comment: Sources: Literature
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Marked gene: SP9 as ready
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Phenotypes for gene: SP9 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, SP9-related
Genetic Epilepsy v0.2199 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Genetic Epilepsy v0.2199 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2198 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Penetrance for gene: SP9 were set to Incomplete
Review for gene: SP9 was set to GREEN
Added comment: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Sources: Literature
Mendeliome v1.1511 MEI4 Lisa Norbart edited their review of gene: MEI4: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1511 MEI4 Lisa Norbart changed review comment from: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature; to: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature
Genetic Epilepsy v0.2198 CCDC88C Rylee Peters reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1511 CCDC88C Rylee Peters reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1511 RHOXF1 Zornitza Stark Marked gene: RHOXF1 as ready
Mendeliome v1.1511 RHOXF1 Zornitza Stark Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1511 RHOXF1 Zornitza Stark Classified gene: RHOXF1 as Amber List (moderate evidence)
Mendeliome v1.1511 RHOXF1 Zornitza Stark Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.184 CELSR1 Chern Lim edited their review of gene: CELSR1: Changed rating: GREEN
Hydrops fetalis v0.308 CELSR1 Chern Lim edited their review of gene: CELSR1: Changed rating: GREEN
Mendeliome v1.1510 MEI4 Zornitza Stark Marked gene: MEI4 as ready
Mendeliome v1.1510 MEI4 Zornitza Stark Gene: mei4 has been classified as Green List (High Evidence).
Mendeliome v1.1510 RHOXF1 Chris Ciotta gene: RHOXF1 was added
gene: RHOXF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RHOXF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RHOXF1 were set to PMID: 38258527
Phenotypes for gene: RHOXF1 were set to Spermatogenic failure, MONDO:0004983, RHOXF1-related
Review for gene: RHOXF1 was set to AMBER
Added comment: In a cohort of 1,201 men from China with oligozoospermia and azoospermia, hemizygous RHOXF1 variants were identified in 4 unrelated individuals.

Three of these variants were missense variants (V130M, A91V & A156V), all were absent from gnomAD (including version 4) and had deleterious in silicos.

The one other variant was a nonsense variant (R160X) which is predicted to escape NMD and truncate the protein. This is seen in gnomAD version 4 in 1 heterozygote female, and absent in other versions.

In vitro functional evidence for these variants was provided, the V130M, A156V and R160X mutants demonstrated impaired protein localisation with an increase in the protein in the cytoplasm and impaired nuclear entry, the A91V mutant protein did not share these localisation defects.

Further, The V130M mutant protein decreased DMRT1 promotor activity, DMRT1 is considered essential for testicular development and spermatogenesis. However, the R160X variant demonstrated increased activation, three times higher than WT. The two other missense variants had no effect.
Sources: Literature
Mendeliome v1.1510 PRDM6 Elena Savva Marked gene: PRDM6 as ready
Mendeliome v1.1510 PRDM6 Elena Savva Gene: prdm6 has been classified as Green List (High Evidence).
Mendeliome v1.1510 PRDM6 Elena Savva Classified gene: PRDM6 as Green List (high evidence)
Mendeliome v1.1510 PRDM6 Elena Savva Gene: prdm6 has been classified as Green List (High Evidence).
Mendeliome v1.1509 PRDM6 Elena Savva gene: PRDM6 was added
gene: PRDM6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRDM6 were set to 38071433; 27716515; 27181681
Phenotypes for gene: PRDM6 were set to Patent ductus arteriosus 3 MIM#617039
Review for gene: PRDM6 was set to GREEN
Added comment: Gene is established for patent ductus arteriosus. Only missense reported but supported by functional studies suggesting LOF.

PMID: 38071433 - Two families (3 affected, 6 affected) with patent ductus arteriosus with/without additional coarctation of the aorta. Family 1 had a missense, family 2 had a PTC - both regarded as VUSs

Additional papers PMID: 27716515;27181681 describe nonsyndromic patent ductus arteriosus for the first time
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.133 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction.
3 patients had renal anomalies including 1 with unilateral cystic kidney disease; and nephritis, and kidney hypoplasia resulting in renal failure in two patients.
All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1508 MEI4 Zornitza Stark Classified gene: MEI4 as Green List (high evidence)
Mendeliome v1.1508 MEI4 Zornitza Stark Gene: mei4 has been classified as Green List (High Evidence).
Mendeliome v1.1507 MEI4 Lisa Norbart gene: MEI4 was added
gene: MEI4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEI4 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MEI4 were set to 38252283
Phenotypes for gene: MEI4 were set to Infertility disorder, MONDO:0005047, MEI4-related
Review for gene: MEI4 was set to GREEN
Added comment: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature
Hydrops fetalis v0.308 CELSR1 Ain Roesley Phenotypes for gene: CELSR1 were changed from Lymphatic malformation 9, MIM# 619319 to Lymphatic malformation 9, MIM# 619319
Hydrops fetalis v0.307 CELSR1 Ain Roesley changed review comment from: Comment on phenotypes: Presentation of hydrod is a phenotypic expansion on Lymphatic malformation; to: Comment on phenotypes: Presentation of hydrops is a phenotypic expansion on Lymphatic malformation
Hydrops fetalis v0.307 CELSR1 Ain Roesley Marked gene: CELSR1 as ready
Hydrops fetalis v0.307 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.307 CELSR1 Ain Roesley Added comment: Comment on phenotypes: Presentation of hydrod is a phenotypic expansion on Lymphatic malformation
Hydrops fetalis v0.307 CELSR1 Ain Roesley Phenotypes for gene: CELSR1 were changed from hydrops fetalis (MONDO:0015193), CELSR1-related to Lymphatic malformation 9, MIM# 619319
Mendeliome v1.1507 WDR44 Seb Lunke Marked gene: WDR44 as ready
Mendeliome v1.1507 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well established.
Mendeliome v1.1507 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Hydrops fetalis v0.306 CELSR1 Ain Roesley Classified gene: CELSR1 as Green List (high evidence)
Hydrops fetalis v0.306 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v1.1507 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Mendeliome v1.1507 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.184 PIEZO1 Naomi Baker reviewed gene: PIEZO1: Rating: RED; Mode of pathogenicity: None; Publications: PMID:38184690; Phenotypes: Prune belly syndrome (MONDO:0007032), PIEZO1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.184 WDR44 Seb Lunke Marked gene: WDR44 as ready
Fetal anomalies v1.184 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well established.
Fetal anomalies v1.184 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.184 CELSR1 Ain Roesley Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770
Fetal anomalies v1.184 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Fetal anomalies v1.184 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.183 CELSR1 Ain Roesley Classified gene: CELSR1 as Green List (high evidence)
Fetal anomalies v1.183 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v1.1506 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Fetal anomalies v1.182 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Marked gene: SAMD7 as ready
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Classified gene: SAMD7 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Marked gene: SH2B3 as ready
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Gene: sh2b3 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Classified gene: SH2B3 as Green List (high evidence)
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Gene: sh2b3 has been classified as Green List (High Evidence).
Mendeliome v1.1506 SAMD7 Zornitza Stark Marked gene: SAMD7 as ready
Mendeliome v1.1506 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Ciliopathies v1.47 WDR44 Seb Lunke Marked gene: WDR44 as ready
Ciliopathies v1.47 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well supported.
Ciliopathies v1.47 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Mendeliome v1.1506 SAMD7 Zornitza Stark Classified gene: SAMD7 as Green List (high evidence)
Mendeliome v1.1506 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Ciliopathies v1.47 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Ciliopathies v1.47 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.85 SH2B3 Ain Roesley gene: SH2B3 was added
gene: SH2B3 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: SH2B3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SH2B3 were set to 37206266; 23908464; 38152053; 37206266; 38152053
Phenotypes for gene: SH2B3 were set to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Review for gene: SH2B3 was set to GREEN
gene: SH2B3 was marked as current diagnostic
Added comment: PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO

- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes

PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3

PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCs
Sources: Literature
Fetal anomalies v1.182 CELSR1 Chern Lim reviewed gene: CELSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38272662; Phenotypes: hydrops fetalis (MONDO:0015193), CELSR1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hydrops fetalis v0.305 CELSR1 Chern Lim gene: CELSR1 was added
gene: CELSR1 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELSR1 were set to 38272662
Phenotypes for gene: CELSR1 were set to hydrops fetalis (MONDO:0015193), CELSR1-related
Review for gene: CELSR1 was set to AMBER
gene: CELSR1 was marked as current diagnostic
Added comment: PMID: 38272662:
- Het de novo missense variants in two unrelated cases of fetal pleural effusions leading to severe fetal hydrops - Cys1318Tyr, Cys1349Arg.
- Both variants lie within the same protein domain.
- Functional studies performed for only one of the variants, p.(Cys1318Tyr): the variant affected CELSR1 protein cell membrane localisation compared with wild-type CELSR1 protein in both a plasmid-based overexpression system and the patient fibroblast cells. Bulk RNA-seq of RNA samples extracted from the proband and the mother’s fibroblast cells demonstrated that in the proband mRNA samples, the amount of CELSR1 mRNA was significantly decreased.
- No functional testing was performed on the p.(Cys1349Arg) variant.
Sources: Literature
Mendeliome v1.1505 SH2B3 Ain Roesley Phenotypes for gene: SH2B3 were changed from Predisposition to haematological malignancies to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Mendeliome v1.1504 SH2B3 Ain Roesley Publications for gene: SH2B3 were set to 26457647; 23908464; 31102422; 31173385
Mendeliome v1.1503 SH2B3 Ain Roesley Mode of inheritance for gene: SH2B3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ciliopathies v1.46 WDR44 Andrew Fennell changed review comment from: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recaptulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature; to: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Ciliopathies v1.46 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recaptulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1502 SH2B3 Ain Roesley Deleted their comment
Mendeliome v1.1502 SH2B3 Ain Roesley commented on gene: SH2B3: PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO

- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes

PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3

PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCs
Mendeliome v1.1502 SH2B3 Ain Roesley reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37206266, 23908464, 38152053; Phenotypes: Myeloproliferation and multi-organ autoimmunity, juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1502 SAMD7 Paul De Fazio gene: SAMD7 was added
gene: SAMD7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMD7 were set to 38272031
Phenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166
Review for gene: SAMD7 was set to GREEN
gene: SAMD7 was marked as current diagnostic
Added comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51.

Four variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.43 SAMD7 Paul De Fazio gene: SAMD7 was added
gene: SAMD7 was added to Macular Dystrophy/Stargardt Disease. Sources: Literature
Mode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMD7 were set to 38272031
Phenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166
Review for gene: SAMD7 was set to GREEN
gene: SAMD7 was marked as current diagnostic
Added comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51.

Four variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays.
Sources: Literature
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Classified gene: CAMK2D as Amber List (moderate evidence)
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Gene: camk2d has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Classified gene: CAMK2D as Amber List (moderate evidence)
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Gene: camk2d has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2197 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Genetic Epilepsy v0.2197 CAMK2D Elena Savva Gene: camk2d has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2197 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to AMBER
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Mendeliome v1.1502 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Mendeliome v1.1502 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Mendeliome v1.1502 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Mendeliome v1.1502 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.177 CAMK2D Elena Savva changed review comment from: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature; to: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Mendeliome v1.1501 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Cardiomyopathy_Paediatric v0.177 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to GREEN
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5682 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to PMID: 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to GREEN
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Mendeliome v1.1500 ERG Zornitza Stark Phenotypes for gene: ERG were changed from Lymphatic malformation 14, MIM# 620602 to Lymphatic malformation 14, MIM# 620602; Myelodysplasia syndrome, MONDO:0018881, ERG-related
Bone Marrow Failure v1.84 ERG Zornitza Stark Phenotypes for gene: ERG were changed from https://ash.confex.com/ash/2023/webprogram/Paper191986.html to Myelodysplasia syndrome, MONDO:0018881, ERG-related
Bone Marrow Failure v1.83 ERG Zornitza Stark Publications for gene: ERG were set to
Bone Marrow Failure v1.82 ERG Zornitza Stark edited their review of gene: ERG: Changed phenotypes: Myelodysplasia syndrome, MONDO:0018881, ERG-related
Mendeliome v1.1499 ERG Zornitza Stark edited their review of gene: ERG: Changed rating: AMBER; Changed publications: s://ash.confex.com/ash/2023/webprogram/Paper191986.html; Changed phenotypes: Myelodysplasia syndrome, MONDO:0018881, ERG-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.82 ERG Zornitza Stark edited their review of gene: ERG: Changed publications: https://ash.confex.com/ash/2023/webprogram/Paper191986.html
Bone Marrow Failure v1.82 ERG Zornitza Stark changed review comment from: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lympheedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature; to: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lymphoedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature
Bone Marrow Failure v1.82 ERG Zornitza Stark Marked gene: ERG as ready
Bone Marrow Failure v1.82 ERG Zornitza Stark Gene: erg has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.82 ERG Zornitza Stark Classified gene: ERG as Amber List (moderate evidence)
Bone Marrow Failure v1.82 ERG Zornitza Stark Gene: erg has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.81 ERG Zornitza Stark gene: ERG was added
gene: ERG was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: ERG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ERG were set to https://ash.confex.com/ash/2023/webprogram/Paper191986.html
Review for gene: ERG was set to AMBER
Added comment: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lympheedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature
Mendeliome v1.1499 RBMX Zornitza Stark Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555
Mendeliome v1.1498 RBMX Zornitza Stark Publications for gene: RBMX were set to 25256757; 34260915
Mendeliome v1.1497 RBMX Zornitza Stark edited their review of gene: RBMX: Added comment: PMID 37277488: In-frame deletion reported in a large multiplex Swedish family; Changed publications: 25256757, 34260915, 37277488; Changed phenotypes: Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238, Gustavson syndrome, MIM# 309555
Intellectual disability syndromic and non-syndromic v0.5681 RBMX Zornitza Stark Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555
Intellectual disability syndromic and non-syndromic v0.5680 RBMX Zornitza Stark Publications for gene: RBMX were set to 25256757; 34260915
Intellectual disability syndromic and non-syndromic v0.5679 RBMX Zornitza Stark edited their review of gene: RBMX: Added comment: PMID 37277488: In-frame deletion reported in a large multiplex Swedish family; Changed publications: 25256757, 34260915, 37277488; Changed phenotypes: Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238, Gustavson syndrome, MIM# 309555
Genetic Epilepsy v0.2196 LMX1B Elena Savva Marked gene: LMX1B as ready
Genetic Epilepsy v0.2196 LMX1B Elena Savva Gene: lmx1b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2196 LMX1B Elena Savva gene: LMX1B was added
gene: LMX1B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LMX1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LMX1B were set to Focal segmental glomerulosclerosis 10 MIM#256020; Nail-patella syndrome MIM#161200
Review for gene: LMX1B was set to RED
Added comment: GeneReviews - Epilepsy was reported in 6% of affected individuals in one large study [Sweeney et al 2003].

No new literature describing SNVs in this gene and epilepsy/seizures.

Gene was listed on Oliver's list
Sources: Literature
Genetic Epilepsy v0.2195 LMNB2 Elena Savva gene: LMNB2 was added
gene: LMNB2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMNB2 were set to PMID: 33783721; 25954030; 34466237
Phenotypes for gene: LMNB2 were set to ?Epilepsy, progressive myoclonic, 9 MIM#616540
Review for gene: LMNB2 was set to AMBER
Added comment: PMID: 33783721 - hom missense p.(Arg158Trp) in a proband with Progressive myoclonus epilepsies. No functional studies to validate the missense variant

PMID: 25954030 - hom missense p.(His157Tyr) in a proband with Progressive myoclonus epilepsies. In vitro assembly analysis of mutant lamin B2 protein revealed a distinct defect in the assembly of the highly ordered fibrous arrays typically formed by wild-type lamin B2, variant segregated in the affected sister

PMID: 34466237 - Hom missense p.(Arg158Leu) in a 5yo boy with progressive wide-based ataxic gait and intractable myoclonic seizure. All unaffected relatives (13) were het or wildtype

Association to epilepsy is amber and biallelic
Seizures noted as a rare feature of dominant disease in OMIM
Sources: Literature
Genetic Epilepsy v0.2194 L2HGDH Elena Savva Classified gene: L2HGDH as Green List (high evidence)
Genetic Epilepsy v0.2194 L2HGDH Elena Savva Gene: l2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2193 L2HGDH Elena Savva Classified gene: L2HGDH as Green List (high evidence)
Genetic Epilepsy v0.2193 L2HGDH Elena Savva Gene: l2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2192 L2HGDH Elena Savva Marked gene: L2HGDH as ready
Genetic Epilepsy v0.2192 L2HGDH Elena Savva Gene: l2hgdh has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2192 L2HGDH Elena Savva gene: L2HGDH was added
gene: L2HGDH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: L2HGDH were set to PMID: 37113859
Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria MIM#236792
Review for gene: L2HGDH was set to GREEN
Added comment: PMID: 37113859 - two sisters with a hom PTC, features included delayed milestones, both had generalised tonic clonic seizures associated with fever in childhood. Reviews literature, notes seizures observed in 26% of patients
Sources: Literature
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Classified gene: KRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Gene: krit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Classified gene: KRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Gene: krit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2190 KRIT1 Elena Savva Marked gene: KRIT1 as ready
Genetic Epilepsy v0.2190 KRIT1 Elena Savva Gene: krit1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2190 KRIT1 Elena Savva gene: KRIT1 was added
gene: KRIT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KRIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KRIT1 were set to 35836010; 35444609
Phenotypes for gene: KRIT1 were set to Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations MIM#116860; Cavernous malformations of CNS and retina MIM#116860; Cerebral cavernous malformations-1 MIM#116860
Review for gene: KRIT1 was set to GREEN
Added comment: Seizures noted as a feature in OMIM

PMID: 35836010 - proband presenting with seizures, nausea and vomiting, tachycardia, and bulging fontanelles

PMID: 35444609 - Family with CCM, segregated extensively. Only a single relative had seizures, but infrequently. Review, notes ~60% of individuals with cavernous hemangioma will experience seizures

GeneReviews - "The cumulative incidence of childhood seizures is ~20% (~60% by age 80 yrs)."
Sources: Literature
Genetic Epilepsy v0.2189 KMT2B Elena Savva Marked gene: KMT2B as ready
Genetic Epilepsy v0.2189 KMT2B Elena Savva Gene: kmt2b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2189 KMT2B Elena Savva gene: KMT2B was added
gene: KMT2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2B were set to PMID: 34477219; 37309110
Phenotypes for gene: KMT2B were set to Dystonia 28, childhood-onset MIM#617284; Intellectual developmental disorder, autosomal dominant 68 MIM#619934
Review for gene: KMT2B was set to RED
Added comment: PMID: 34477219 - Single 30yo patient with a canonical splice variant resulting in inframe exon 8 skipping. Presented with adult-onset cerebellar ataxia, minor dystonia, neuropathy and seizure

PMID: 37309110 - large review study, no patients specified to have seizures/epilepsy

Gene was listed in the Oliver review
Sources: Literature
Genetic Epilepsy v0.2188 KMT2A Elena Savva Classified gene: KMT2A as Green List (high evidence)
Genetic Epilepsy v0.2188 KMT2A Elena Savva Gene: kmt2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2188 KMT2A Elena Savva Classified gene: KMT2A as Green List (high evidence)
Genetic Epilepsy v0.2188 KMT2A Elena Savva Gene: kmt2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2187 KMT2A Elena Savva Marked gene: KMT2A as ready
Genetic Epilepsy v0.2187 KMT2A Elena Savva Gene: kmt2a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2187 KMT2A Elena Savva gene: KMT2A was added
gene: KMT2A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2A were set to PMID: 37075569
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome MIM#605130
Review for gene: KMT2A was set to GREEN
Added comment: OMIM notes seizures were observed in a single patient

PMID: 37075569 - couldnt access paper, but abstract notes five patients with DEE, where epilepsy ranged from drug resistant to self-limited. Reviews literature and notes 33 patients with epilepsy, but limited clinical details.
Sources: Literature
Mendeliome v1.1497 MCTS1 Zornitza Stark Phenotypes for gene: MCTS1 were changed from Inherited susceptibility to mycobacterial diseases, MONDO:0019146, MCTS1-related to Immunodeficiency 118, mycobacteriosis, MIM# 301115
Mendeliome v1.1496 MCTS1 Zornitza Stark edited their review of gene: MCTS1: Changed phenotypes: Immunodeficiency 118, mycobacteriosis, MIM# 301115
Hereditary Neuropathy - complex v1.10 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Intellectual disability syndromic and non-syndromic v0.5679 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Mendeliome v1.1496 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Lipodystrophy_Lipoatrophy v1.14 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Lipodystrophy_Lipoatrophy v1.13 PLA2G16 Zornitza Stark edited their review of gene: PLA2G16: Changed rating: GREEN; Changed phenotypes: Lipodystrophy, familial partial, type 9, MIM# 620683; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2186 KDM6A Elena Savva Marked gene: KDM6A as ready
Genetic Epilepsy v0.2186 KDM6A Elena Savva Gene: kdm6a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2186 KDM6A Elena Savva gene: KDM6A was added
gene: KDM6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KDM6A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: KDM6A were set to PMID: 28442529
Phenotypes for gene: KDM6A were set to Kabuki syndrome 2 MIM#300867
Review for gene: KDM6A was set to RED
Added comment: PMID: 28442529 - describes generalized epilepsy with febrile seizures plus in a family with a co-segregating SCN1A variant. Proband had GEFS+, dysmorphic facial features, short stature, developmental delay, and intellectual disability.

Gene was on the Oliver list
Sources: Literature
Genetic Epilepsy v0.2185 KDM5A Elena Savva Marked gene: KDM5A as ready
Genetic Epilepsy v0.2185 KDM5A Elena Savva Gene: kdm5a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2185 KDM5A Elena Savva gene: KDM5A was added
gene: KDM5A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KDM5A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDM5A were set to PMID: 34210021
Phenotypes for gene: KDM5A were set to Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Review for gene: KDM5A was set to RED
Added comment: PMID: 34210021 - large multigene deletion in a family with ID, epilepsy and schizophrenia. This gene and CACNA1C were considered the best candidates.

No evidence of SNVs in this gene causing epilepsy. This gene was on the Oliver list
Sources: Literature
Mendeliome v1.1495 KDM5A Elena Savva Phenotypes for gene: KDM5A were changed from autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Genetic Epilepsy v0.2184 KATNB1 Elena Savva gene: KATNB1 was added
gene: KATNB1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KATNB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KATNB1 were set to PMID: 26640080
Phenotypes for gene: KATNB1 were set to Lissencephaly 6, with microcephaly MIM#616212
Review for gene: KATNB1 was set to RED
Added comment: PMID: 26640080 - Proband with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. Seizures developed by 6mo, had a homozygous canonical splice deletion

PMID: 31484711 - describes patients with seizures (epilepsy was documented in 69%) from a cohort with subcortical heterotopic gray matter malformations, but unclear which were specific for this gene
Sources: Literature
Genetic Epilepsy v0.2183 KAT6A Elena Savva Marked gene: KAT6A as ready
Genetic Epilepsy v0.2183 KAT6A Elena Savva Gene: kat6a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2183 KAT6A Elena Savva Classified gene: KAT6A as Green List (high evidence)
Genetic Epilepsy v0.2183 KAT6A Elena Savva Gene: kat6a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2182 KAT6A Elena Savva gene: KAT6A was added
gene: KAT6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KAT6A were set to PMID: 34748993
Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome MIM#616268
Review for gene: KAT6A was set to GREEN
Added comment: PMID: 34748993 - 2 new probands with KAT6A syndrome and epilepsy.
Proband 1 - Epilepsy onset was at 3 months of age when daily right hemiclonic seizures appeared in sleep. Had a de novo missense, previously reported as pathogenic.
Proband 2 - Seizures onset was at 5 months with daily clusters of symmetric spasms characterized by flexion of the arms, extension of the legs and eyes’ rolling. Had a de novo PTC

Paper then reviews literature, notes 17/90 probands had epilepsy
Sources: Literature
Genetic Epilepsy v0.2181 KANSL1 Elena Savva Classified gene: KANSL1 as Green List (high evidence)
Genetic Epilepsy v0.2181 KANSL1 Elena Savva Gene: kansl1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2180 KANSL1 Elena Savva Marked gene: KANSL1 as ready
Genetic Epilepsy v0.2180 KANSL1 Elena Savva Gene: kansl1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2180 KANSL1 Elena Savva gene: KANSL1 was added
gene: KANSL1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KANSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KANSL1 were set to PMID: 28440867
Phenotypes for gene: KANSL1 were set to Koolen-De Vries syndrome MIM#610443
Review for gene: KANSL1 was set to GREEN
Added comment: GeneReviews: describes seizures/epilepsy as a less common trait, where OMIM notes its in 50% of cases.

PMID: 28440867 - Median age at seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after onset. Focal impaired awareness seizures were the most frequent seizure type occurring in 20 of 31, usually with prominent autonomic features.
Sources: Literature
Genetic Epilepsy v0.2179 JMJD1C Elena Savva Classified gene: JMJD1C as Amber List (moderate evidence)
Genetic Epilepsy v0.2179 JMJD1C Elena Savva Gene: jmjd1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2178 JMJD1C Elena Savva Classified gene: JMJD1C as Amber List (moderate evidence)
Genetic Epilepsy v0.2178 JMJD1C Elena Savva Gene: jmjd1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2177 JMJD1C Elena Savva Marked gene: JMJD1C as ready
Genetic Epilepsy v0.2177 JMJD1C Elena Savva Gene: jmjd1c has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2177 JMJD1C Elena Savva gene: JMJD1C was added
gene: JMJD1C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: JMJD1C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JMJD1C were set to PMID: 32996679; 26181491; 31954878
Phenotypes for gene: JMJD1C were set to Intellectual disability (MONDO#0001071), JMJD1C-related
Review for gene: JMJD1C was set to AMBER
Added comment: PMID: 32996679 - de novo synonymous variant resulting in a 21bp deletion, who had learning disability and myoclonic epilepsy (onset 10yo).
Paper reviews prev reports, notes only 1/19 other patients with seizures (p.P163L)

PMID: 26181491 - de novo p.P163L (same as above), in a proband with gait dyspraxia, hand-washing stereotype, learning impairment, teeth grinding, air swallowing, kyphoscoliosis, and tonic epilepsy. Functional studies support missense pathogenicity.

PMID: 31954878 - 2/7 patients with de novo variants with ASD, ID and seizures. One proband had a de novo missense (p.V117I), another a PTC (p.P109Lfs*3) of unknown inheritance
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5678 JMJD1C Elena Savva Phenotypes for gene: JMJD1C were changed from Intellectual disability to Intellectual disability (MONDO#0001071), JMJD1C-related
Mendeliome v1.1494 JMJD1C Elena Savva Phenotypes for gene: JMJD1C were changed from Intellectual disability to Intellectual disability (MONDO#0001071), JMJD1C-related
Genetic Epilepsy v0.2176 JARID2 Elena Savva gene: JARID2 was added
gene: JARID2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JARID2 were set to PMID: 22480366
Phenotypes for gene: JARID2 were set to Developmental delay with variable intellectual disability and dysmorphic facies MIM#620098
Review for gene: JARID2 was set to RED
Added comment: PMID: 22480366 - part of a larger multigene deletion, where a patient had seizures.

No patients with seizures reported with SNVs, but on the Oliver list as a gene to be considered.
Sources: Literature
Genetic Epilepsy v0.2175 ITGB4 Elena Savva Marked gene: ITGB4 as ready
Genetic Epilepsy v0.2175 ITGB4 Elena Savva Gene: itgb4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2175 ITGB4 Elena Savva gene: ITGB4 was added
gene: ITGB4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ITGB4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGB4 were set to Epidermolysis bullosa, junctional 5A, intermediate MIM#619816; Epidermolysis bullosa, junctional 5B, with pyloric atresia MIM#226730
Review for gene: ITGB4 was set to RED
Added comment: No reports of seizures/epilepsy in probands with biallelic variants in this gene
Sources: Literature
Genetic Epilepsy v0.2174 INTS8 Elena Savva Marked gene: INTS8 as ready
Genetic Epilepsy v0.2174 INTS8 Elena Savva Gene: ints8 has been classified as Red List (Low Evidence).
Red cell disorders v1.24 PKLR Zornitza Stark Mode of inheritance for gene: PKLR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v1.23 PKLR Zornitza Stark edited their review of gene: PKLR: Added comment: Only single family for the mono-allelic condition.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Classified gene: CRELD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Mendeliome v1.1493 MEIOB Zornitza Stark Phenotypes for gene: MEIOB were changed from Spermatogenic failure 22 MIM#617706; primary ovarian insufficiency to Spermatogenic failure 22 MIM#617706; Premature ovarian failure 23, MIM# 620686
Mendeliome v1.1492 MEIOB Zornitza Stark Publications for gene: MEIOB were set to 34794894; 24068956; 31000419; 28206990
Mendeliome v1.1491 MEIOB Zornitza Stark reviewed gene: MEIOB: Rating: GREEN; Mode of pathogenicity: None; Publications: 35991565, 34392356, 31000419; Phenotypes: Premature ovarian failure 23, MIM# 620686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2174 INTS8 Elena Savva gene: INTS8 was added
gene: INTS8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: INTS8 were set to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity MIM#618572
Review for gene: INTS8 was set to RED
Added comment: No published evidence associating this gene and epilepsy
Sources: Literature
Genetic Epilepsy v0.2173 IBA57 Elena Savva Marked gene: IBA57 as ready
Genetic Epilepsy v0.2173 IBA57 Elena Savva Gene: iba57 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2173 IBA57 Elena Savva gene: IBA57 was added
gene: IBA57 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IBA57 were set to PMID: 30258207
Phenotypes for gene: IBA57 were set to Multiple mitochondrial dysfunctions syndrome 3 MIM#615330
Review for gene: IBA57 was set to RED
Added comment: PMID: 30258207 - girl with developmental regression and spastic quadriplegia. Brain MRI at 8 months showed cerebral white matter involvement, periventricular rarefaction, and corpus callosum involvement. She developed febrile seizures at the age of 18 months.
Chet missense pair found, no functional studies to support pathogenicity
Sources: Literature
Genetic Epilepsy v0.2172 IARS2 Elena Savva Marked gene: IARS2 as ready
Genetic Epilepsy v0.2172 IARS2 Elena Savva Gene: iars2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2172 IARS2 Elena Savva gene: IARS2 was added
gene: IARS2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: IARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS2 were set to PMID: 30041933
Phenotypes for gene: IARS2 were set to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia MIM#616007
Review for gene: IARS2 was set to RED
Added comment: PMID: 30041933 - Japanese sibling pair presented with Leigh syndrome and infantile spasms. The siblings were identified with compound heterozygous missense mutations p.[(Phe227Ser)];[(Arg817His)]. No functional studies to support the pathogenicity of the missense variants
Sources: Literature
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Classified gene: OPA3 as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.23 OPA3 Bryony Thompson gene: OPA3 was added
gene: OPA3 was added to Gastrointestinal neuromuscular disease. Sources: Literature
Mode of inheritance for gene: OPA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA3 were set to 31119193
Phenotypes for gene: OPA3 were set to Optic atrophy 3 MONDO:0008133
Mode of pathogenicity for gene: OPA3 was set to Other
Review for gene: OPA3 was set to GREEN
gene: OPA3 was marked as current diagnostic
Added comment: 11 of the 12 affected individuals from 3 families with OPA3 missense (p.Met8Thr, & p.Gln105Glu) had possible or confirmed gastrointestinal dysmotility symptoms as a feature of the condition. Haploinsufficiency is not expected to be the mechanism of disease. Gain of function or dominant negative effect have been suggested mechanisms of disease.
Sources: Literature
Mitochondrial disease v0.915 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Mitochondrial disease v0.915 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.9 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Hereditary Neuropathy - complex v1.9 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.9 OPA3 Bryony Thompson Classified gene: OPA3 as Green List (high evidence)
Hereditary Neuropathy - complex v1.9 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.8 OPA3 Bryony Thompson gene: OPA3 was added
gene: OPA3 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: OPA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA3 were set to 31119193; 28050599
Phenotypes for gene: OPA3 were set to Optic atrophy 3 MONDO:0008133
Mode of pathogenicity for gene: OPA3 was set to Other
Review for gene: OPA3 was set to GREEN
gene: OPA3 was marked as current diagnostic
Added comment: Peripheral neuropathy has been reported in multiple individuals with ADOA associated with OPA3. Haploinsufficiency is not expected to be the mechanism of disease. Gain of function or dominant negative effect have been suggested mechanisms of disease.
PMID: 31119193 - 9 of the 12 affected individuals from 3 families with OPA3 missense (p.Met8Thr, & p.Gln105Glu) had a possible or confirmed peripheral neuropathy. Was presenting feature in a single case.
PMID: 28050599 - de novo c.235C>G p.(Leu79Val) identified in a woman who presented with cataracts, optic atrophy, lipodystrophy/lipoatrophy, and peripheral neuropathy.
Sources: Literature
Mitochondrial disease v0.915 OPA3 Bryony Thompson Phenotypes for gene: OPA3 were changed from to 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR; Optic atrophy 3 with cataract (MIM#165300), AD
Mitochondrial disease v0.914 OPA3 Bryony Thompson Publications for gene: OPA3 were set to
Mitochondrial disease v0.913 OPA3 Bryony Thompson Mode of inheritance for gene: OPA3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Gene: opa3 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Classified gene: OPA3 as Red List (low evidence)
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Gene: opa3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Marked gene: DHX16 as ready
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Gene: dhx16 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Classified gene: DHX16 as Green List (high evidence)
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Gene: dhx16 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Marked gene: DOHH as ready
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Phenotypes for gene: ECHS1 were changed from Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; Leigh syndrome MONDO:0009723; cerebral palsy MONDO:0006497; paroxysmal dystonia MONDO:0016058 to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277
Genetic Epilepsy v0.2168 ECHS1 Zornitza Stark Classified gene: ECHS1 as Green List (high evidence)
Genetic Epilepsy v0.2168 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2167 EED Zornitza Stark Marked gene: EED as ready
Genetic Epilepsy v0.2167 EED Zornitza Stark Gene: eed has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2167 EED Zornitza Stark Classified gene: EED as Red List (low evidence)
Genetic Epilepsy v0.2167 EED Zornitza Stark Gene: eed has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Phenotypes for gene: ECM1 were changed from Urbach-Wiethe disease, MIM# 247100 to Urbach-Wiethe disease, MIM# 247100
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Marked gene: ECM1 as ready
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Phenotypes for gene: ECM1 were changed from to Urbach-Wiethe disease, MIM# 247100
Genetic Epilepsy v0.2165 ECM1 Zornitza Stark Classified gene: ECM1 as Green List (high evidence)
Genetic Epilepsy v0.2165 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2164 ECM1 Zornitza Stark reviewed gene: ECM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Urbach-Wiethe disease, MIM# 247100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2164 KARS Zornitza Stark Marked gene: KARS as ready
Genetic Epilepsy v0.2164 KARS Zornitza Stark Gene: kars has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2164 KARS Zornitza Stark Phenotypes for gene: KARS were changed from to Leukoencephalopathy, progressive, infantile-onset, with or without deafness MIM#619147
Genetic Epilepsy v0.2163 KARS Zornitza Stark Publications for gene: KARS were set to
Genetic Epilepsy v0.2162 KARS Zornitza Stark Mode of inheritance for gene: KARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1491 NEPRO Zornitza Stark Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Mendeliome v1.1490 NEPRO Zornitza Stark Classified gene: NEPRO as Green List (high evidence)
Mendeliome v1.1490 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Mendeliome v1.1489 NEPRO Zornitza Stark reviewed gene: NEPRO: Rating: GREEN; Mode of pathogenicity: None; Publications: 37294112; Phenotypes: Anauxetic dysplasia 3, MIM618853; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Marked gene: NEPRO as ready
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Skeletal dysplasia v0.261 NEPRO Zornitza Stark Classified gene: NEPRO as Green List (high evidence)
Skeletal dysplasia v0.261 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Stroke v1.14 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Stroke v1.14 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Stroke v1.14 JAM3 Zornitza Stark Classified gene: JAM3 as Green List (high evidence)
Stroke v1.14 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Stroke v1.13 JAM3 Zornitza Stark gene: JAM3 was added
gene: JAM3 was added to Stroke. Sources: Expert Review
Mode of inheritance for gene: JAM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM3 were set to 23255084; 21109224
Phenotypes for gene: JAM3 were set to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Review for gene: JAM3 was set to GREEN
Added comment: Autosomal recessive disorder with a distinctive phenotype comprising haemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Affected individuals have a catastrophic neurologic clinical course resulting in death in infancy.

Four unrelated families reported.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v1.80 COL12A1 Elena Savva Publications for gene: COL12A1 were set to 28306229; 31273343; 24334604
Aortopathy_Connective Tissue Disorders v1.79 COL12A1 Elena Savva reviewed gene: COL12A1: Rating: ; Mode of pathogenicity: None; Publications: 37458870, 37353357; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Marked gene: RNF213 as ready
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Gene: rnf213 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Phenotypes for gene: RNF213 were changed from {Moyamoya disease 2, susceptibility to} to susceptibility to Moyamoya disease 2, (MIM# 607151)
Cerebral vascular malformations v0.36 RNF213 Zornitza Stark Publications for gene: RNF213 were set to 21048783
Cerebral vascular malformations v0.35 RNF213 Zornitza Stark Mode of inheritance for gene: RNF213 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1489 RNF213 Zornitza Stark Publications for gene: RNF213 were set to
Mendeliome v1.1488 RNF213 Zornitza Stark Mode of inheritance for gene: RNF213 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.410 MYOCD Zornitza Stark Classified gene: MYOCD as Amber List (moderate evidence)
Congenital Heart Defect v0.410 MYOCD Zornitza Stark Gene: myocd has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.409 MYOCD Zornitza Stark edited their review of gene: MYOCD: Added comment: Single family with bi-allelic disease reported, which seems to be more severe expression of the mono-allelic disease, hence the Amber (rather than Red) rating.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.5676 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type MIM#616462 to Acrofacial dysostosis, Cincinnati type MIM#616462; Leukodystrophy, hypomyelinating, 27, MIM# 620675
Leukodystrophy - paediatric v0.304 POLR1A Zornitza Stark changed review comment from: Further two unrelated patients reported.; to: Further two unrelated patients reported but overall two homozygous missense variants only.
Leukodystrophy - paediatric v0.304 POLR1A Zornitza Stark edited their review of gene: POLR1A: Changed rating: AMBER
Leukodystrophy - paediatric v0.304 POLR1A Zornitza Stark Classified gene: POLR1A as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.304 POLR1A Zornitza Stark Gene: polr1a has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.303 POLR1A Zornitza Stark Classified gene: POLR1A as Green List (high evidence)
Leukodystrophy - paediatric v0.303 POLR1A Zornitza Stark Gene: polr1a has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.302 POLR1A Zornitza Stark edited their review of gene: POLR1A: Added comment: Further two unrelated patients reported.; Changed rating: GREEN; Changed publications: 36917474
Intellectual disability syndromic and non-syndromic v0.5675 POLR1A Zornitza Stark Mode of inheritance for gene: POLR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5674 POLR1A Zornitza Stark reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.302 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Leukodystrophy MONDO:0019046, POLR1A related to Leukodystrophy, hypomyelinating, 27, MIM# 620675
Leukodystrophy - paediatric v0.301 POLR1A Zornitza Stark reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1487 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type, (MIM#616462); Leukodystrophy MONDO:0019046, POLR1A-related to Leukodystrophy, hypomyelinating, 27, MIM# 620675; Acrofacial dysostosis, Cincinnati type, (MIM#616462)
Mendeliome v1.1486 POLR1A Zornitza Stark edited their review of gene: POLR1A: Changed phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675, Acrofacial dysostosis, Cincinnati type, (MIM#616462)
Mendeliome v1.1486 PCYT1A Zornitza Stark Phenotypes for gene: PCYT1A were changed from Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940; Congenital lipodystrophy to Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940; Lipodystrophy, congenital generalized, type 5, MIM# 620680
Mendeliome v1.1485 PCYT1A Zornitza Stark edited their review of gene: PCYT1A: Changed phenotypes: Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940, Lipodystrophy, congenital generalized, type 5, MIM# 620680
Lipodystrophy_Lipoatrophy v1.13 PCYT1A Zornitza Stark Phenotypes for gene: PCYT1A were changed from Congenital lipodystrophy; fatty liver disease to Lipodystrophy, congenital generalized, type 5, MIM# 620680
Lipodystrophy_Lipoatrophy v1.12 PCYT1A Zornitza Stark edited their review of gene: PCYT1A: Changed phenotypes: Lipodystrophy, congenital generalized, type 5, MIM# 620680
Optic Atrophy v1.27 SPG7 Elena Savva commented on gene: SPG7: PMID: 32548275 - fs reported in AD optic atrophy where in NMD-predicted regions of the protein, were either isolated cases (1 proband) or segregated in a single family (2 affected).
**Several families with missense variants had more extensive segregation within families, and one was de novo - this is in ANOTHER gene, NOT SPG7
Intellectual disability syndromic and non-syndromic v0.5674 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5673 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Genetic Epilepsy v0.2161 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5673 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-related to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Genetic Epilepsy v0.2161 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Mendeliome v1.1485 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Ataxia - paediatric v1.18 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Skeletal dysplasia v0.260 NEPRO Achchuthan Shanmugasundram reviewed gene: NEPRO: Rating: GREEN; Mode of pathogenicity: None; Publications: 37294112; Phenotypes: Anauxetic dysplasia 3, OMIM:618853; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1484 TREX1 Zornitza Stark Mode of inheritance for gene: TREX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Marked gene: EIF2AK2 as ready
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Green List (high evidence)
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.31 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Neurodegeneration with brain iron accumulation v0.30 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.542 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Regression v0.541 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1483 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Hemochromatosis, type 5, MIM# 615517; Neuroferritinopathy (MONDO:0011638) to Hemochromatosis, type 5, MIM# 615517; Neurodegeneration with brain iron accumulation 9, MIM# 620669
Cerebellar and Pontocerebellar Hypoplasia v1.64 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Cerebellar and Pontocerebellar Hypoplasia v1.63 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1482 IRF1 Zornitza Stark Phenotypes for gene: IRF1 were changed from Inherited susceptibility to mycobacterial disease, MONDO:0019146, IRF1-related to Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Mendeliome v1.1481 IRF1 Zornitza Stark edited their review of gene: IRF1: Changed phenotypes: Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Ataxia - adult onset v1.6 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Ataxia - adult onset v1.6 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Ataxia - adult onset v1.6 COQ4 Zornitza Stark Classified gene: COQ4 as Green List (high evidence)
Ataxia - adult onset v1.6 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Ataxia - adult onset v1.5 COQ4 Zornitza Stark gene: COQ4 was added
gene: COQ4 was added to Ataxia - adult onset. Sources: Expert Review
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to 36047608; 38014483; 38013626
Phenotypes for gene: COQ4 were set to Spastic ataxia 10, autosomal recessive, MIM# 620666
Review for gene: COQ4 was set to GREEN
Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.
Sources: Expert Review
Ataxia - paediatric v1.17 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 30225196, 33704555, 30847826, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mitochondrial disease v0.912 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Spastic ataxia 10, autosomal recessive, MIM# 620666
Mitochondrial disease v0.911 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 25658047; 26185144; 33704555
Mitochondrial disease v0.910 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 25658047, 26185144, 33704555, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1481 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1480 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 25658047; 26185144; 33704555
Mendeliome v1.1479 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 25658047, 26185144, 33704555, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1479 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Neutropaenia to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Immunodeficiency, common variable, 15, MIM# 620670; Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674
Mendeliome v1.1478 SEC61A1 Zornitza Stark Publications for gene: SEC61A1 were set to 27392076; 32325141; 28782633
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Added comment: PMID 32325141: single individual with de novo missense and phenotype primarily characterised by severe neutropenia.; Changed publications: 27392076, 32325141, 28782633, 32325141
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670, Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674
Phagocyte Defects v1.25 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Neutropaenia to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674; Immunodeficiency, common variable, 15, MIM# 620670
Phagocyte Defects v1.24 SEC61A1 Zornitza Stark Classified gene: SEC61A1 as Green List (high evidence)
Phagocyte Defects v1.24 SEC61A1 Zornitza Stark Gene: sec61a1 has been classified as Green List (High Evidence).
Phagocyte Defects v1.23 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed rating: GREEN
Phagocyte Defects v1.23 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Added comment: PMID 32325141: single individual with de novo missense and phenotype primarily characterised by severe neutropenia.

PMID 28782633: 11 individuals with primarily CVID phenotype, including neutropenia.; Changed publications: 27392076, 32325141, 28782633, 32325141; Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674, Immunodeficiency, common variable, 15, MIM# 620670
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670
Common Variable Immunodeficiency v1.12 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from hypogammaglobulinemia; common variable immunodeficiency to Immunodeficiency, common variable, 15, MIM# 620670
Common Variable Immunodeficiency v1.11 SEC61A1 Zornitza Stark Classified gene: SEC61A1 as Green List (high evidence)
Common Variable Immunodeficiency v1.11 SEC61A1 Zornitza Stark Gene: sec61a1 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v1.10 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Added comment: Further 11 individuals from two families reported in PMID: 28782633 with immunological phenotype.; Changed publications: 28782633
Common Variable Immunodeficiency v1.10 SEC61A1 Zornitza Stark reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency, common variable, 15, MIM# 620670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Predominantly Antibody Deficiency v0.132 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Severe recurrent respiratory tract infections to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Immunodeficiency, common variable, 15, MIM# 620670
Predominantly Antibody Deficiency v0.131 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670
Genetic Epilepsy v0.2159 KPNA7 Elena Savva Phenotypes for gene: KPNA7 were changed from severe neurodevelopmental defects; epilepsy to Neurodevelopmental disorder (MONDO#0700092), KPNA7-related
Mendeliome v1.1477 KPNA7 Elena Savva Phenotypes for gene: KPNA7 were changed from Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder to Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder (MONDO#0700092), KPNA7-related
Genetic Epilepsy v0.2158 KIF4A Elena Savva Publications for gene: KIF4A were set to 24812067; 34346154
Genetic Epilepsy v0.2158 KIF4A Elena Savva Classified gene: KIF4A as Amber List (moderate evidence)
Genetic Epilepsy v0.2158 KIF4A Elena Savva Gene: kif4a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2157 KIF4A Elena Savva reviewed gene: KIF4A: Rating: ; Mode of pathogenicity: None; Publications: PMID: 36482480, 24812067, 34346154; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5672 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Mendeliome v1.1476 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923; Taurodontism, microdontia, and dens invaginatus (MIM#313490) to Intellectual developmental disorder, X-linked 100 MIM#300923; Taurodontism, microdontia, and dens invaginatus MIM#313490
Hydrocephalus_Ventriculomegaly v0.121 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Genetic Epilepsy v0.2157 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Genetic Epilepsy v0.2156 KIF1BP Elena Savva Classified gene: KIF1BP as Red List (low evidence)
Genetic Epilepsy v0.2156 KIF1BP Elena Savva Gene: kif1bp has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2155 KIF1BP Elena Savva reviewed gene: KIF1BP: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 28277559; Phenotypes: Goldberg-Shprintzen megacolon syndrome, MIM#609460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5671 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2155 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.1475 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5670 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Intellectual disability to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Genetic Epilepsy v0.2154 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Neurodevelopmental disorder (MONDO#0700092), KCTD13-related to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Genetic Epilepsy v0.2154 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Mendeliome v1.1474 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Intellectual disability; seizures to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Hypertrichosis syndromes v0.46 KCNN3 Elena Savva Classified gene: KCNN3 as Amber List (moderate evidence)
Hypertrichosis syndromes v0.46 KCNN3 Elena Savva Gene: kcnn3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5669 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3 MIM#618658
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva Marked gene: KCNN3 as ready
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva Gene: kcnn3 has been classified as Red List (Low Evidence).
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva gene: KCNN3 was added
gene: KCNN3 was added to Hypertrichosis syndromes. Sources: Literature
Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNN3 were set to 34907639
Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3 MIM#618658
Review for gene: KCNN3 was set to AMBER
Added comment: PMID: 34907639 - literature review of previous ZLS patients, describes hypertrichosis as mild/moderate on trunk and limbs (3/7), or synophrys (4/7) in all patients
Sources: Literature
Mendeliome v1.1473 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3; MIM#618658
Genetic Epilepsy v0.2153 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome to Zimmermann-Laband syndrome 3 MIM#618658
Genetic Epilepsy v0.2153 KCNN3 Elena Savva Publications for gene: KCNN3 were set to PMID: 33594261
Genetic Epilepsy v0.2152 KCNN3 Elena Savva reviewed gene: KCNN3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34907639; Phenotypes: Zimmermann-Laband syndrome 3 MIM#618658; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2152 KCNAB3 Elena Savva Publications for gene: KCNAB3 were set to PMID: 32990398
Mendeliome v1.1472 KCNAB3 Elena Savva Publications for gene: KCNAB3 were set to PMID: 32990398
Genetic Epilepsy v0.2151 KCNAB3 Elena Savva reviewed gene: KCNAB3: Rating: RED; Mode of pathogenicity: None; Publications: 37396552, 32990398, 36345448; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.1471 KCNAB3 Elena Savva reviewed gene: KCNAB3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 37396552, 32990398, 36345448; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2151 KCNAB3 Elena Savva Phenotypes for gene: KCNAB3 were changed from febrile seizures; afebrile seizure; genetic epilepsy with febrile seizures plus to Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related
Mendeliome v1.1471 KCNAB3 Elena Savva Phenotypes for gene: KCNAB3 were changed from febrile seizures; afebrile seizure; genetic epilepsy with febrile seizures plus to Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related
Genetic Epilepsy v0.2150 KARS Elena Savva reviewed gene: KARS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33942428; Phenotypes: Leukoencephalopathy, progressive, infantile-onset, with or without deafness MIM#619147; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5668 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Genetic Epilepsy v0.2150 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Mendeliome v1.1470 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Genetic Epilepsy v0.2149 ECM1 Andrew Fennell changed review comment from: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature; to: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature
Genetic Epilepsy v0.2149 EIF2AK2 Andrew Fennell gene: EIF2AK2 was added
gene: EIF2AK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to PMID: 32197074
Phenotypes for gene: EIF2AK2 were set to Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877
Review for gene: EIF2AK2 was set to GREEN
Added comment: PMID: 32197074 - Four individuals (50%) with seizures including GTCS, focal tonic, and focal complex types.

PMID: 33236446 - a single individual with neonatal generalised tonic seizures, dystonia, significant ID and later spasticity.
Sources: Literature
Genetic Epilepsy v0.2149 EED Andrew Fennell gene: EED was added
gene: EED was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EED was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EED were set to PMID: 34533271
Phenotypes for gene: EED were set to Cohen-Gibson syndrome, MIM# 617561
Review for gene: EED was set to RED
Added comment: PMID: 34533271 - single case report of child with absence epilepsy aged 5yrs and subsequent GTC seizures throughout childhood.

Note, Griffiths et al (2019) reported 1 patient with seizures but later attributed this to hyperinsulinaemic hypoglycaemia.
Sources: Literature
Genetic Epilepsy v0.2149 ECM1 Andrew Fennell gene: ECM1 was added
gene: ECM1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ECM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECM1 were set to PMID: 11929856; 28434238
Review for gene: ECM1 was set to GREEN
Added comment: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature
Genetic Epilepsy v0.2149 ECHS1 Andrew Fennell gene: ECHS1 was added
gene: ECHS1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECHS1 were set to PMID: 29575569; 35098523
Phenotypes for gene: ECHS1 were set to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; Leigh syndrome MONDO:0009723; cerebral palsy MONDO:0006497; paroxysmal dystonia MONDO:0016058
Review for gene: ECHS1 was set to GREEN
Added comment: PMID: 29575569 - 4 of 4 patients with Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1) had seizures onset in infancy.

PMID: 35098523 - single case report of an infant with Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency with status epilepticus after propofol administration.
Sources: Literature
Genetic Epilepsy v0.2149 DOHH Andrew Fennell gene: DOHH was added
gene: DOHH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 30661771; 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: PMID: 35858628 - three of the five reported individuals with this neurodevelopmental disorder identified to have seizures. Two individuals had febrile seizures in mid-childhood with one going on to have generalised epilepsy. A third individual had generalised epilepsy.

PMID: 30661771 - Of note, DOHH is a key part of the same two-step enzymatic pathway as DHPS which is also associated with a neurodevelopmental disorder that prominently features seizures.
Sources: Literature
Genetic Epilepsy v0.2149 DHX16 Andrew Fennell gene: DHX16 was added
gene: DHX16 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DHX16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX16 were set to PMID: 31256877; 36211162
Phenotypes for gene: DHX16 were set to Neuromuscular disease and ocular or auditory anomalies with or without seizures, MIM# 618733
Review for gene: DHX16 was set to GREEN
Added comment: PMID: 31256877 - two of the four reported individuals had seizures (infantile spasms in one & GTC in one)

PMID: 36211162 - single case report of an 18-month old child with infantile spasms, likely for several months prior to presentation.
Sources: Literature
Motor Neurone Disease v1.8 DNAJC7 Sarah Leigh reviewed gene: DNAJC7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31768050, 35039179, 34233860, 32897108, 37870677, 35456894; Phenotypes: amyotrophic lateral sclerosis; Mode of inheritance: None
Ciliary Dyskinesia v1.38 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Congenital nystagmus v1.19 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Overgrowth v1.11 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Overgrowth v1.11 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2149 PRIMA1 Chris Ciotta gene: PRIMA1 was added
gene: PRIMA1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRIMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIMA1 were set to PMID: 26339676
Phenotypes for gene: PRIMA1 were set to Frontal Lobe Epilepsy MONDO:0002612
Review for gene: PRIMA1 was set to RED
Added comment: - 2/3 siblings from unaffected parents in PMID: 26339676 were diagnosed with nocturnal frontal lobe epilepsy, which was confirmed by EEG. The affected siblings were homozygous for the c.93+2T>C variant canonical splice site variant. This variant was demonstrated by mini-gene assay to skip exon 2 of PRIMA1.

Overall 1 family, 2 individuals with epilepsy and high impact variants in PRIMA1.
Sources: Literature
Genetic Epilepsy v0.2149 POMGNT2 Chris Ciotta gene: POMGNT2 was added
gene: POMGNT2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POMGNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT2 were set to PMID: 36808730
Phenotypes for gene: POMGNT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8 MIM#614830
Review for gene: POMGNT2 was set to RED
Added comment: This gene was included in the Genes4Epilepsy (PMID: 36808730) Gene resource and was said to be associated with developmental and epileptic encephalopathies and malformations of cortical development. In a review of the literature an association with individuals presenting with epilepsy was not found.
Sources: Literature
Genetic Epilepsy v0.2149 PLXNC1 Chris Ciotta gene: PLXNC1 was added
gene: PLXNC1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PLXNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXNC1 were set to PMID: 36808730
Phenotypes for gene: PLXNC1 were set to Malformations of cortical development
Review for gene: PLXNC1 was set to RED
Added comment: This gene was included in the genes4epilepsy resource (PMID:36808730) and was reported as being associated with the clinical phenotype "malformations of cortical development".

There are no current PubMed articles linking this gene with epilepsy however
Sources: Literature
Genetic Epilepsy v0.2149 PRDM8 Chris Ciotta gene: PRDM8 was added
gene: PRDM8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRDM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM8 were set to PMID: 2296154; 35034233
Phenotypes for gene: PRDM8 were set to ?Epilepsy, progressive myoclonic, 10 MIM#616640
Review for gene: PRDM8 was set to RED
Added comment: - PMID:22961547, 3 individuals from one family, all with myoclonic epilepsy, all had the Phe261Leu variant. This variant is absent from gnomAD V4.

- PMID: 35034233, Two individuals from one family, no clinical seizures but presented with myoclonus and abnormal EEG (generalised epileptiform charges), these individuals had the Ala230Gly missense change, which has currently been reported as a VUS.
Sources: Literature
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta reviewed gene: PPP2R5D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26168268, 29296277, 26576547; Phenotypes: Houge-Janssens syndrome 1 MIM#616355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta Deleted their review
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta gene: PPP2R5D was added
gene: PPP2R5D was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPP2R5D were set to Houge-Janssens syndrome 1 MIM#616355
Review for gene: PPP2R5D was set to GREEN
Added comment: - PMID:26168268, 3/11 individuals with intellectual disability also presented with epilepsy, In these three individuals two had the commonly reported pathogenic Glu198Lys variant while the third had another very well reported Glu200Lys variant.

- PMID:29296277, 2/2 individuals in this study with variants in PPP2R5D with epilepsy. Both individuals had the Glu198Lys variant.

- PMID: 26576547, 1/7 individuals with variants in this gene presented with complex partial seizures, this individual also had the Glu198Lys well reported variant.
Sources: Literature
Genetic Epilepsy v0.2149 POMK Chris Ciotta gene: POMK was added
gene: POMK was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMK were set to PMID: 24925318
Phenotypes for gene: POMK were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 MIM#615249
Review for gene: POMK was set to RED
Added comment: - PMID:24925318, 1/3 unrelated individuals with bi-allelic POMK variants presented with seizures along with Cobblestone lissencephaly and hydrocephalus. This individual was compound heterozgyous for a high impact frameshift variant (c.286delT, p.F96fs) and a missense variant (c.905T>A , p.V302D).
Sources: Literature
Genetic Epilepsy v0.2149 POGZ Chris Ciotta gene: POGZ was added
gene: POGZ was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to PMIS: 34645992; 31136090; 28490548; 26739615; 27824329
Phenotypes for gene: POGZ were set to White-Sutton syndrome MIM#616364
Review for gene: POGZ was set to GREEN
Added comment: - 2/12 Individuals in this in PMID:34645992 with POGZ PTVs were reported as having a history of at least 1 seizure. This information is mentioned in the article but seems to be left out in the clinical characteristics table on page 97 so we are unsure which individuals had a history of seizures.

- PMID:31136090, a de novo POGZ truncating variant (c.2711T>G; p.Leu904*) in an individual with dysmorphic features and poor tolerance to oral feeding. No family history of seizures or ID. First epileptic seizure occurred at age 2 and persisted despite clobazam. MRI at age 3 showed cortical and sub cortical atrophy and individual presented with dev delay and epileptic encephalopathy.

- PMID: 28480548, 15 year old female with healthy parents, MRI revealed global cerebellar atrophy, individual presented with dev delay and no verbal capacity, was being treated for epilepsy with medication. p.Asn941fs*3 variant was identified in this individual.

- PMID:26739615, 5 individuals with POGZ p.Ser278* variant, only 1/5 with complex, partial seizures.

- PMID:27824329, One chinese individual with autism, POGZ variant p.Gln127* who presented with seizures.

All the above variants are high impact and absent from gnomAD V4. 6 unique cases of individuals with high impact POGZ variants presenting with seizures/epilepsy.
Sources: Literature
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Classified gene: POLG2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2148 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 MIM#610131; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2147 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Genetic Epilepsy v0.2147 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2146 POLG2 Chris Ciotta gene: POLG2 was added
gene: POLG2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLG2 were set to PMID: 21555342
Phenotypes for gene: POLG2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 MIM#610131
Review for gene: POLG2 was set to AMBER
Added comment: PMID:21555342 reports 4/11 unrelated individuals with mitochondrial disease as presenting with seizures and heterozygous variants in POLG2, 3/4 of these individuals had missense variants. Of these variants, 2 have been reported in Clinvar as benign and have high homozygote counts in gnomAD V4. The p.P205R variant was seen in an individual with seizures and is absent from gnomAD V4 and has been reported as pathogenic once in ClinVar for MIM#610131.

The last individual with seizures had a high impact variant (p.L475DfsX2) with 3 heterozygotes in the population (V4) which has been classified as pathogenic in ClinVar.

Overall, 2/11 unrelated individuals with plausible pathogenic variants presenting with seizures.
Sources: Literature
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2145 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy. One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Mendeliome v1.1469 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Mendeliome v1.1469 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Mendeliome v1.1469 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Mendeliome v1.1469 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Mendeliome v1.1468 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy.

One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5666 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy.

One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Genetic Epilepsy v0.2144 PLP1 Lisa Norbart gene: PLP1 was added
gene: PLP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PLP1 were set to 7512350; 11071483; 21679407; 28133555; 29486744; 35346287; 37637647
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher Disease, MIM#312080
Review for gene: PLP1 was set to GREEN
Added comment: PMID: 7512350 (1994) - Mouse study demonstrating that seizures and convulsions are a result of a 2-fold increased PLP gene dosage. (Cited in OMIM)

PMID: 11071483 (2000) - One family with 2x brothers affected with PMD, both developing seizures in late teens. Other symptoms in both brothers include hypotonia at birth, nystagmus, and slowly progressive spastic paraplegia. (Cited in OMIM)

PMID: 21679407 (2011) - Male cohort, 43 individuals from 38 unrelated families with a PLP1-related disorder diagnosis. Seizures present in 2/43 males (both PLP1 duplication mutations). Additional symptoms include 3/43 stridor, 4/43 developmental delay, and 18/43 muscular hypotonia.

PMID: 28133555 (2017) - Case report on 9 year old male affected with classic PMD. Presented with a history of seizures since age 4. Also presents with developmental delay, nystagmus, microcephaly, spastic quadriplegia. Maternally inherited gain of 436Kb on Xq22.2 encompassing TCEAL1,MORF4L2, PLP1, and RAB9B, of which only PLP1 is associated with a disease.

PMID: 29486744 (2018) - Case report on family diagnosed with connatal PMD (previously diagnosed as X-linked epileptic seizures). The PLP1 missense mutation p.Ala84Asp was found to segregate in the family. 1x proband presenting with daily generalised seizures, onset at 8 months and no treatment response. 2x cousins and 2x maternal uncles also presented with epilepsy, all onset around 6 months and all died in childhood. Additional symptoms include 5/5 hypotonia and 5/5 psycho-motor delay. Consanguinity reported in the family.

PMID: 35346287 (2022) - Chinese cohort of 141 patients, 111 whom were followed up with. Seizures present in 4/28 individuals with connatal PMD, including 1 patient who died due to epileptic seizures at age 7, and 4/56 individuals with transitional PMD. Additional symptoms include 111/111 development delay, 110/111 nystagmus, 93/111 hypotonia, 35/111 stridor, and 4/111 respiratory difficulty.

PMID: 37637647 (2023) - Case report on 1x newborn individual diagnosed with failure to thrive and later PMD. Presented with episodes of rapid eye and side-to-side head movement episodes of 5-10 seconds, onset one month after birth. Diagnosis of seizure disorder considered before further testing. Individual hemizygous for PLP1: c.67G>A (p.Gly23Arg), maternally inherited.

GeneReviews: Seizures may develop in infants affected by 'severe connatal PMD'.
Sources: Literature
Leukodystrophy - paediatric v0.301 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Leukodystrophy - paediatric v0.301 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.301 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Leukodystrophy - paediatric v0.300 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Leukodystrophy - paediatric v0.300 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to 30635937 35527102; https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2143 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to 30635937 35527102; https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2142 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2141 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Genetic Epilepsy v0.2141 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Mendeliome v1.1467 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Mendeliome v1.1467 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Mendeliome v1.1467 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Mendeliome v1.1466 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Mendeliome v1.1466 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Ataxia - paediatric v1.17 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Ataxia - paediatric v1.17 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Ataxia - paediatric v1.17 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Ataxia - paediatric v1.17 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Fetal anomalies v1.182 MAX Zornitza Stark Marked gene: MAX as ready
Fetal anomalies v1.182 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Fetal anomalies v1.182 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Fetal anomalies v1.182 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Marked gene: MAX as ready
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Polydactyly v0.270 MAX Zornitza Stark Marked gene: MAX as ready
Polydactyly v0.270 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Polydactyly v0.270 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Polydactyly v0.270 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Mendeliome v1.1465 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300 to {Pheochromocytoma, susceptibility to}, MIM# 171300; Syndromic disease (MONDO:0002254), MAX-related
Mendeliome v1.1464 MAX Zornitza Stark Publications for gene: MAX were set to 21685915
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Marked gene: MAX as ready
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Gene: max has been classified as Amber List (Moderate Evidence).
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Classified gene: MAX as Amber List (moderate evidence)
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Gene: max has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Marked gene: SCN2A as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Classified gene: SCN2A as Green List (high evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Clefting disorders v0.246 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Clefting disorders v0.246 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Clefting disorders v0.246 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Clefting disorders v0.246 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.269 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Polydactyly v0.269 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Polydactyly v0.269 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Polydactyly v0.269 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2140 TSPYL1 Zornitza Stark Publications for gene: TSPYL1 were set to 32885560; 15273283; 33075815
Overgrowth v1.11 SPIN4 Zornitza Stark Mode of inheritance for gene: SPIN4 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1463 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Mendeliome v1.1463 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1463 SPIN4 Zornitza Stark Mode of inheritance for gene: SPIN4 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1462 SPIN4 Zornitza Stark Classified gene: SPIN4 as Amber List (moderate evidence)
Mendeliome v1.1462 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Overgrowth v1.10 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Overgrowth v1.10 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2139 CP Zornitza Stark Marked gene: CP as ready
Genetic Epilepsy v0.2139 CP Zornitza Stark Gene: cp has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2139 CP Zornitza Stark Classified gene: CP as Amber List (moderate evidence)
Genetic Epilepsy v0.2139 CP Zornitza Stark Gene: cp has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.299 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Leukodystrophy - paediatric v0.299 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.299 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Leukodystrophy - paediatric v0.299 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Microcephaly v1.248 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Microcephaly v1.248 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Microcephaly v1.248 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Microcephaly v1.248 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1461 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Mendeliome v1.1461 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1461 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Mendeliome v1.1461 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.180 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Fetal anomalies v1.180 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.180 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Fetal anomalies v1.180 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1460 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Mendeliome v1.1460 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1460 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Mendeliome v1.1460 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1459 CACHD1 Zornitza Stark reviewed gene: CACHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: syndromic complex neurodevelopmental disorder MONDO:0800439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1459 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Leukodystrophy - paediatric v0.298 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Genetic Epilepsy v0.2138 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Ataxia - paediatric v1.16 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Fetal anomalies v1.179 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5661 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Polydactyly v0.268 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Macrocephaly_Megalencephaly v0.137 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to AMBER
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Mendeliome v1.1459 MAX Rylee Peters reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38141607; Phenotypes: Syndromic disease (MONDO:0002254), MAX-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v1.10 SPIN4 Zornitza Stark Classified gene: SPIN4 as Amber List (moderate evidence)
Overgrowth v1.10 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1459 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Mendeliome v1.1459 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Mendeliome v1.1459 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Mendeliome v1.1459 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.37 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to AMBER
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited

Only 2x probands with microphthalmia and/or optic disc coloboma.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Optic Atrophy v1.27 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Optic Atrophy v1.27 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Optic Atrophy v1.27 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Optic Atrophy v1.27 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.259 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Mendeliome v1.1458 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Mendeliome v1.1458 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Clefting disorders v0.245 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Pituitary hormone deficiency v0.33 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Mendeliome v1.1458 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Mendeliome v1.1458 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.7 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Muscle biopsy of the right medial gastrocnemius at age 1 demonstrated mild variation in fiber size with scattered, moderately small, rounded polyhedral fibers of both types. There were no significant dystrophic features.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Regression v0.541 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Regression v0.541 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Fetal anomalies v1.179 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Mendeliome v1.1457 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.54 SCN2A Ee Ming Wong gene: SCN2A was added
gene: SCN2A was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN2A were set to 38097767
Phenotypes for gene: SCN2A were set to Alternating hemiplegia of childhood MONDO:0016241, SCN2A-related
Review for gene: SCN2A was set to GREEN
gene: SCN2A was marked as current diagnostic
Added comment: - 1x in-frame del and 2x missense variants identified in three individuals with typical alternating
hemiplegia of childhood (2x confirmed de novo, 1x unknown inheritance)
- Loss of function demonstrated by functional studies of all three variants (mutant transcripts transfected into HEK293T cells showed either complete loss of function or altered electrophysiological properties)
Sources: Literature
Holoprosencephaly and septo-optic dysplasia v1.9 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Regression v0.541 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Regression v0.541 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Fetal anomalies v1.179 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: PMID: 38158856 - Six affected individuals from four unrelated families with homozygous CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant). Excluding the two fatal cases, all other were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Seizure was reported in one case. Whole exome sequencing identified bi-allelic loss of function variants in the CACHD1 gene. In vitro human neural models of CACHD1 depletion displayed dysregulated of Wnt signaling in the developing brain.
Sources: Literature
Polydactyly v0.268 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Leukodystrophy - paediatric v0.298 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Mendeliome v1.1457 SPIN4 Belinda Chong gene: SPIN4 was added
gene: SPIN4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPIN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SPIN4 were set to 36927955
Phenotypes for gene: SPIN4 were set to Lui-Jee-Baron syndrome MIM#301114
Review for gene: SPIN4 was set to AMBER
Added comment: PMID 36927955
* Single family, hemizygous frameshift variant (NM_001012968.3, c.312_313AGdel) identified in a male individual with generalized overgrowth of prenatal onset, variant also present in the mother and grandmother (both had adult heights 2 SDS greater than their midparental heights).
* In vitro shows loss of function and mice studies recapitulated the human phenotype with
generalized overgrowth, including increased longitudinal bone growth.
Sources: Literature
Sources: Literature
Leukodystrophy - paediatric v0.298 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Regression v0.540 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 TSPYL1 Lilian Downie reviewed gene: TSPYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36082874; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome MIM#608800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5660 SOX8 Paul De Fazio changed review comment from: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted).
Sources: Literature; to: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Optic Atrophy v1.26 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Mendeliome v1.1457 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Mendeliome v1.1457 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: PMID: 38158856 - Six affected individuals from four unrelated families with homozygous CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant). Excluding the two fatal cases, all other were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Seizure was reported in one case. Whole exome sequencing identified bi-allelic loss of function variants in the CACHD1 gene. In vitro human neural models of CACHD1 depletion displayed dysregulated of Wnt signaling in the developing brain.
Sources: Literature
Overgrowth v1.9 SPIN4 Belinda Chong gene: SPIN4 was added
gene: SPIN4 was added to Overgrowth. Sources: Literature
Mode of inheritance for gene: SPIN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SPIN4 were set to 36927955
Phenotypes for gene: SPIN4 were set to Lui-Jee-Baron syndrome MIM#301114
Review for gene: SPIN4 was set to AMBER
gene: SPIN4 was marked as current diagnostic
Added comment: PMID 36927955
* Single family, hemizygous frameshift variant (NM_001012968.3, c.312_313AGdel) identified in a male individual with generalized overgrowth of prenatal onset, variant also present in the mother and grandmother (both had adult heights 2 SDS greater than their midparental heights).
* In vitro shows loss of function and mice studies recapitulated the human phenotype with
generalized overgrowth, including increased longitudinal bone growth.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted).
Sources: Literature
Mendeliome v1.1457 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Optic Atrophy v1.26 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Leukodystrophy - paediatric v0.298 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 CP Lilian Downie gene: CP was added
gene: CP was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CP were set to PMID: 32741407, PMID: 18200628
Phenotypes for gene: CP were set to Hemosiderosis, systemic, due to aceruloplasminemia MIM#604290
Review for gene: CP was set to AMBER
Added comment: Reports of patients x3 with seizures as part of this phenotype.
***This is an adult onset brain iron accumulation neurodegenerative disorder***
Sources: Expert list
Regression v0.540 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Regression. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Marked gene: COQ8A as ready
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Classified gene: COQ8A as Green List (high evidence)